Category Archives: Diseases of the blood

Prophylaxis to prevent venous thromboembolism

Prophylactic measures to prevent venous thrombosis during surgery are aimed at procedures for preventing stasis, such as early mobilization, elevation of the legs, compression stockings, and possibly calf-muscle stimulation and passive calf-muscle exercises during surgery, and methods for preventing hypercoagulability, usually using heparin.
Low-risk patients (Table 6.26) require no specific measures other than early mobilization. Moderate-risk patients should receive specific prophylaxis such as low-dose heparin at a dose of 5000 units subcutaneously every 8 or 12 hours until the patient is ambulatory; no laboratory monitoring is required.
Low molecular weight heparin once daily has been shown to be more effective than standard low-dose heparin in preventing thrombosis in high-risk patients. However, in general surgical practice there is no clear evidence that low molecular weight heparin is superior to low-dose heparin and it is much more expensive. Before the introduction of low molecular weight heparin, other approaches were used in high-risk surgical patients such as low-dose warfarin and higher doses of subcutaneous heparin to keep the PTTK between 1.25 and 1.5 times the control value.

Treatment of established venous thromboembolism.

Treatment of established venous thromboembolism.

Treatment of established venous thromboembolism (Information box 6.2) The aim of anticoagulant treatment is to prevent further thrombosis and pulmonary embolization while resolution of venous thrombi occurs by natural fibrinolytic activity. Anticoagulation is started with heparin as it produces an immediate anticoagulant effect. There is no evidence  that it is necessary to use heparin for any longer than it takes for simultaneously administered warfarin to produce an anticoagulant effect, usually about 3-4 days. Anticoagulation for 6 weeks is sufficient for patients after their first thrombosis as long as there are no persisting risk factors. Long-term treatment should be considered in patients with repeated episodes or continuing risk factors. Outpatient anticoagulation is best supervised in anticoagulant clinics. Patients are issued with national booklets for recording INR results and anticoagulant doses. The role of thrombolytic therapy in the treatment of venous thrombosis is not established. It is sometimes used in patients with massive pulmonary embolism and in patients with extensive deep venous thrombi. For these conditions it is necessary to give a bolus dose of streptokinase, 250000 units over 30 min to inactivate antibodies formed by previous streptococcal infection followed by a continuous infusion, approximately 100000 units every hour, for 24-72 hours. The dose of streptokinase is adjusted to maintain the TT between two and four times the control value.
Thrombolytic therapy should be followed by anticoagulation with heparin for a few days and then by oral anticoagulants for a few months to prevent rethrombosis. New agents are being evaluated as antithrombotic agents including direct inhibitors of thrombin such as hirudin. Hirudin can inactivate thrombin bound to fibrin more efficiently than AT-III potentiated by heparin. Clinical studies are required to establish the antithrombotic effect in relation to the risk of bleeding.

Further reading

Bloom Al., Forbes CD, Thomas DP and Tuddenham EGD (1994) Haemostasis and Thrombosis, 2nd edn. Edinburgh: Churchill Livingstone. Chanarin I (1979) The Megablastic Anaemias, 3rd edn.
Oxford: Blackwell Scientific Publications. Dacie ]V (1985 (volume 1), 1988 (volume 2), 1992 (volume 3)) The Haemolytic Anaemias, 3rd edn. Edinburgh:

Churchill Livingstone.

Firkin F, Chesterman C, Pennington D & Rush B (eds) (1989) de Gruchy’s Clinical Haematology in Medical Practice, 5th edn. Oxford: Blackwell Scientific. Furie B & Furie BC (1992) Molecular and cellular biology of blood coagulation. New England Journal of Medicine 326, 800-806.
Groopman JE, Molina JM & Scadden DT (1989) Haemopoietic growth factors: Biology and clinical applications. New England Journal of Medicine 321, 1449- 1459.
Hows JM (1991) Severe aplastic anaemia: The patient without a HLA-identical sibling. British Journal of Haematology 77, 1-4.
Mollison PL, Engelfriet CP & Contreras M (1993) Blood Transfusion in Clinical Medicine, 9th edn. Oxford: Blackwell Scientific Publications.
Pippard MJ, Hughes RT & Cotes PM (1992) Erythropoietin. In: Recent Advances in Haematology 6 (ed. Hoffbrand AV & Brenner MK). Edinburgh: Churchill


Thein SL & Weatherall DJ (1988) The thalassaemias. In: Recent Advances in Haematology 5 (ed. Hoffbrand AV). Edinburgh: Churchill Livingstone. Williams WI, Beutler E, Erslev AJ & Lichtman MA (1990) Hematology, 4th edn. New York: McGraw-Hill.

Prevention and treatment of venous thromboembolism

Venous thromboembolism is a common problem after surgery, particularly in high-risk patients such as elderly patients, those with malignant disease and those with a history of previous thrombosis. The incidence is also high in patients confined to bed following trauma, myocardial infarction or other illnesses. Prevention and treatment of venous thrombosis includes the use of anticoagulants.


HEPARIN is not a single substance but a mixture of polysaccharides. Commercially available un fractionated heparin consists of components with molecular weights varying from 5000 to 35000 and an average of about 13000. It was extracted initially from liver, hence its name, but it is now prepared from porcine gastric mucosa. Heparin has an immediate effect on coagulation by potentiation of the formation of irreversible complexes between AT-III and activated serine protease coagulation factors (thrombin, Xlla, Xla, Xa, IXa and Vila). Low MOLECULARWEIGHT HEPARINS are produced by enzymatic or chemical degradation of standard heparin producing fractions with molecular weights in the range of 2000-8000. Potentiation of thrombin inhibition (anti- IIa activity) requires a minimum length of the heparin molecule with an approximate molecular weight of 5400, whereas the inhibition of factor Xa only requires a smaller heparin molecule with a molecular weight of about 1700. Low molecular weight heparins have the following properties:
1 They have greater activity against factor Xa than against factor IIa, suggesting that they may produce an equivalent anticoagulant effect as standard heparin but have a lower risk of bleeding, although this still awaits confirmation in clinical studies. In addition, low molecular weight heparins cause less inhibition of platelet function.
2 They have a longer half-life than standard heparin and so can be given as a once daily subcutaneous injection instead of every 8-12 hours.
3 They produce little effect on tests of overall coagulation, such as the PTTK at doses recommended for prophylaxis.
4 They are being increasingly used for antithrombotic prophylaxis of high-risk surgical patients. Fixed-dose low molecular weight heparin regimens are being studied for the treatment of established thrombosis. The main complication of treatment with heparin is bleeding. This is managed by stopping heparin. Very occasionally it is necessary to neutralize heparin with protamine. Other complications include osteoporosis with prolonged therapy and thrombocytopenia.
ORAL ANTICOAGULANTS act by interfering with vitamin K metabolism. There are two types of oral anticoagulants, the coumarins and indanediones. The coumarin warfarin is most commonly used because it has a low incidence of side-effects other than bleeding. The dosage is controlled by PT tests. Thromboplastin reagents for PT testing are derived from a variety of sources and give different PT results for the same plasma. It is now standard practice to compare each thromboplastin with an international reference preparation so that they can be assigned an international sensitivity index (tsr). The international normalized ratio (INR) is the ratio of the patient’s PT to a normal control when using the international reference preparation (Information box 6.1).
Each laboratory develops a chart adapted to the ISI of their thromboplastin to convert the patient’s PT to the INR and reports both values. The use of this system :neans that PT tests on a given plasma sample using different thromboplastins result in the same INR and that anticoagulant control is comparable in different hospitals across the world.

Incidence of venous thromboembolism in hospital patients according to risk group

Incidence of venous thromboembolism in hospital patients according to risk group

Therapeutic ranges for oral anticoagulation proposed by the 8ritish Society for Haematology (1990).

Therapeutic ranges for oral anticoagulation proposed by the 8ritish Society for Haematology (1990).

Contraindications to the use of oral anticoagulants are seldom absolute and include:
• Severe hypertension
• Non-thrombo-embolic strokes
• Peptic ulceration
•  Severe liver and renal disease
• Pre-existing haemostatic defects
• pregnancy. Oral anticoagulants should be avoided in pregnancy because they are teratogenic in the first tremester and may be associated with fetal haernorgerhage later in pregnancy. When anticoagulation is considered essential in pregnancy, self-administered subcotaneous heparin should be used as an alternative, although this may not be as effective for women with prosthetic cardiac valves. Specialist advice should be sought about anticoagulation in pregnancy. manydrugs interact with warfarin . more frequent PT testing should accompany changes in medication, which should occur with the full knowledge of the anticoagulant clinic.
An increased anticoagulant effect due to warfarin (Emergency box 6.1) is usually produced by:
• Drugs causing a reduction in the metabolism of warfarin include tricyclic antidepressants, cimetidine, sulphonamides, phenothiazines and amiodarone .
• Drugs such as clofibrate and quinidine increase the sensitivity of hepatic receptors to warfarin.
• Drugs interfering with vitamin K absorption (such as broad-spectrum antibiotics and cholestyramine) may also potentiate the action of warfarin.
• The displacement of warfarin from its binding site on serum albumin by drugs such as sulphonamides is not usually responsible for clinically important interactions.
• Drugs that inhibit platelet function (such as aspirin) increase the risk of bleeding.
• Alcohol excess, cardiac failure, liver or renal disease, thyrotoxicosis and febrile illnesses may result in potentiation of the effect of warfarin.
A decreased anticoagulant effect due to warfarin is usually produced by drugs that increase the clearance of warfarin by induction of hepatic enzymes that metabolize warfarin, such as rifampicin and barbiturates. Side-effects of warfarin other than bleeding are rare.

Management of over-anticoagulation with warfarin.

Management of over-anticoagulation
with warfarin.


A thrombus is defined as a solid mass formed in the circulation from the constituents of the blood during life. Fragments of thrombi (emboli) may break off and block vessels downstream. Thromboembolic disease is much more common than abnormal bleeding; nearly half of adult deaths in England and Wales are due to coronary artery thrombosis, cerebral artery thrombosis or pulmonary embolism.
A thrombus results from a complex series of events involving coagulation factors, platelets, red blood cells and the vessel wall.

Arterial thrombosis

This usually occurs in association with atheroma, which tends to form at areas of turbulent blood flow such as the bifurcation of arteries. Platelets adhere to the damaged vascular endothelium and aggregate in response to ADP and TXA2 to form a ‘white thrombus’. The growth of the platelet thrombus is limited at its margins by PGIz. Eventually blood coagulation may be activated at the site of the thrombus, resulting either in complete occlusion of the vessel or embolization that produces distal obstruction. The risk factors for arterial thrombosis are related to the development of atherosclerosis.
Arterial thrombi may form in the heart, as mural thrombi in the left ventricle after myocardial infarction, in the left atrium in mitral valve disease or on the surfaces of prosthetic valves.

Venous thrombosis

Unlike arterial thrombosis, venous thrombosis often occurs in normal vessels. Important causes are stasis and hypercoagulability. The majority of venous thrombi occur in the deep veins of the leg, originating around the valves as ‘red thrombi’ consisting mainly of red cells and fibrin. The propagating thrombus is formed of fibrin and platelets and is particularly liable to embolize. Chronic venous obstruction in the deep veins of the leg results in a permanently swollen limb and may lead to ulceration (postphlebitic syndrome). Risk factors for venous thrombosis are shown. Both arterial and venous thrombosis may occur with changes in blood cells such as polycythaemia, thrombocythaemia and sickle cell anaemia. The clinical features and diagnosis of venous thrombosis are discussed.


Thrombophilia is a term describing inherited or acquired defects of haemostasis leading to a predisposition to venous or arterial thrombosis. It should be considered in patients with:
• Recurrent venous thrombosis
• Venous thrombosis for the first time under 40
• A family history of venous thrombosis
• An unusual venous thrombosis such as mesenteric vein thrombosis
• eonatal thrombosis
• Recurrent abortions
• Arterial thrombosis in the absence of arterial disease Laboratory investigation of such patients includes:
• Full blood count including platelet count
• Coagulation screen including a fibrinogen level
• Screen for a coagulation factor inhibitor including a lupus anticoagulant
• Assays for naturally occurring anticoagulants such as AT-III, protein C and protein S
• Tests of the fibrinolytic pathway

Risk factors for venous thromboembolism.

Risk factors for venous thromboembolism.

Prevention and treatment of arterial thrombosis

Attempts to prevent or reduce arterial thrombosis are mainly directed at minimizing factors predisposing to atherosclerosis. Treatment of established arterial thrombosis includes the use of antiplatelet drugs and thrombolytic therapy.

Antiplatelet drugs

Platelet activation at the site of vascular damage is crucial to the development of arterial thrombosis, and this can be altered by the following drugs:
ASPIRIN inhibits the enzyme cyclo-oxygenase and this results in reduced platelet production of TXA2•.
DIPYRIDAMOLE, which inhibits platelet phosphodiesterase causing an increase in cyclic AMP with potentiation of the action of PGI2, has been widely used as an anti thrombotic agent but there is little evidence that it is effective.
The indications for and results of antiplatelet therapy are discussed in the appropriate sections.

Thrombolytic therapy

STREPTOKINASE is a purified fraction of the filtrate obtained from cultures of haemolytic streptococci. It forms a 1:1 complex with plasminogen, resulting in a conformational change in plasminogen, revealing an active site which activates other plasminogen molecules to form plasmin. Streptokinase is given as an infusion of 1 500000 units over 1 hour in acute myocardial infarction.
Laboratory monitoring of such short-term thrombolytic therapy is not necessary.
The main problem with streptokinase is its indiscriminate activation of plasminogen so that both fibrin in clots and free fibrinogen are lysed, leading to low fibrinogen levels and the risk of haemorrhage.

Drugs used in the treatment of thrombotic disorders.

Drugs used in the treatment of thrombotic

ANISOYLATED PLASMINOGEN STREPTOKINASE ACTIVATOR COMPLEX (APSAC) is a complex of plasminogen and an anisoylated form of streptokinase. The complex binds to any fibrin within intravascular clots where the anisoyl group is hydrolysed and the streptokinaseplasminogen complex produces fibrinolysis. The advantage of APSAC over streptokinase is its more sustained duration of action and it is given as a single bolus dose. UROKINASE is produced naturally by the kidney. It cleaves plasminogen directly to produce plasmin.
TISSUE-TYPE PLASMINOGEN ACTIVATOR (t-PA) and single-chain urokinase-type plasminogen activator (scu- PA) are produced using recombinant gene technology. They were claimed to be relatively ‘clot-specific’, i.e. to have a greater affinity for fibrin-bound plasminogen than circulating plasminogen, and therefore to cause less systemic fibrinolysis and bleeding than streptokinase. However, the use of these newer thrombolytic agents has not yet been shown to produce fewer bleeding episodes than streptokinase. An accelerated dosage schedule of t- PA seems to produce a more rapid restoration of coronary flow.
THROMBOLYTIC THERAPY. The indications for and results of the use of thrombolytic therapy in myocardial infarction are discussed . The combination of aspirin with thrombolytic therapy produces better results than thrombolytic therapy alone.
The main risk of thrombolytic therapy is bleeding and treatment should not be given to patients who have had recent bleeding, uncontrolled hypertension or a stroke, or surgery or other invasive procedures within the previous 10 days.


Vitamin K deficiency

Vitamin K is necessary for the v-carboxylation of glutamic acid residues on factors II, VII, IX and X and on proteins C and S; without it, these factors cannot bind calcium and form complexes with PF-3 to carry out their normal functions.
Deficiency of vitamin K may be due to:
• Inadequate stores, as in haemorrhagic disease of the newborn and protein-energy malnutrition
• Malabsorption of vitamin K, which particularly occurs in cholestatic jaundice as it is a fat-soluble vitamin
• Oral anticoagulant drugs, which are vitamin K antagonists The PT and PTTK are prolonged and there may be bruising, haematuria and gastrointestinal or cerebral bleeding. Minor bleeding is treated with phytomenadione (vitamin K,) 10 mg intravenously. Some correction of the PT is usual within 6 hours but it may not return to normal for 2 days.
Newborn babies have low levels of vitamin K, and this may cause minor bleeding in the first week of life (classical haemorrhagic disease of the newborn). Vitamin K deficiency may also cause late haemorrhagic disease of the newborn which occurs between 2 and 26 weeks after birth and may result in severe bleeding such as intracranial haemorrhage. Most infants with these syndromes have been exclusively breastfed and both may be prevented by administering 1 mg intramuscular vitamin K to all neonates.
There has been recent concern that the administration of intramuscular vitamin K is associated with the development of cancer in childhood but the evidence for the association is not conclusive and further studies will be needed to resolve the uncertainty.

Liver disease

Liver disease may result in a number of defects in haemostasis:
VITAMIN K DEFICIENCY due to intra- or extra-hepatic cholestasis.
REDUCED SYNTHESIS of coagulation factors due to severe hepatocellular damage. The use of vitamin K does not improve the results of abnormal coagulation tests, but it is generally given because of the accompanying malabsorption.
THROMBOCYTOPENIA may result from hypersplenism due to splenomegaly associated with portal hypertension.
FUNCTIONAL ABNORMALITIES of platelets and fibrinogen are found in many patients with liver failure.
DISSEMINATED INTRAVASCULAR COAGULATION may occur in acute liver failure.

Disseminated intravascular coagulation

There is widespread generation of fibrin within blood vessels, due to activation of the extrinsic pathway by release of coagulant material, activation of the intrinsic pathway y diffuse endothelial damage or generalized platelet aggregation.
There is consumption of platelets and coagulation facrs and secondary activation of fibrinolysis leading to roduction of FOPs, which may contribute to the coagution defect by inhibiting fibrin polymerization.

Disseminated intravascular coagulation. FDP, fibrin degradation products.

Disseminated intravascular coagulation. FDP, fibrin degradation products.


These are numerous and include Gram-negative and meningococcal septicaemia, disseminated malignant disease, haemolytic transfusion reactions, obstetric conditions such as abruptio placentae and amniotic fluid embolism, widespread tissue damage after trauma, burns or surgery, falciparum malaria and snalce bites.


The underlying disorder is usually obvious. The patient is often acutely ill and shocked. The clinical presentation of Ole varies from no bleeding at all to complete haemostatic failure with widespread haemorrhage. Bleeding may occur from the mouth, nose and venepuncture sites and there may be widespread ecchymoses.
Thrombotic events may occur as a result of vessel occlusion by fibrin and platelets; any organ may be involved but the skin and kidneys are most often affected.


The diagnosis is often suggested by the underlying condition of the patient. In severe cases with haemorrhage, the PT, PTTK and TT are usually very prolonged and the fibrinogen level markedly reduced. High levels of FOPs are found due to the intense fibrinolytic activity stimulated by the presence of fibrin in the circulation. There is severe thrombocytopenia and the blood film may show fragmented red blood cells. In mild cases without bleeding, increased synthesis of coagulation factors and platelets may result in normal PT, PTTK, TT and platelet counts, although the FOPs will be raised.


Treatment of the underlying condition is most important and may be all that is necessary in non-bleeding patients. Transfusions of platelet concentrates, FFP, cryoprecipitate and red cell concentrates may be indicated in patients who are bleeding. The use of heparin to prevent intravascular coagulation remains controversial and it is now rarely given. Inhibitors of fibrinolysis such as tranexamic acid should not be used in DIC as dangerous fibrin deposition may result.

Excessive fibrinolysis

Activation of fibrinolysis occurs in DIC as a secondary event in response to intravascular deposition of fibrin. It may also occur during surgery involving tumours of the prostate, breast, pancreas and uterus owing to release of tissue plasminogen activators. Primary hyperfibrinolysis is very rare.
The clinical picture is similar to DIC with widespread bleeding. Laboratory investigations are similar with a prolonged PT, PTTK and TT, a low fibrinogen level, and increased FDPs, although fragmented red cells and thrombocytopenia are not seen as disseminated coagulation is not present.
If the diagnosis is certain, fibrinolytic inhibitors such as s-aminocaproic acid (EACA) or tranexamic acid should be considered. If DIC cannot be excluded, it is safer to treat as for DIC.
Massive transfusion Stored blood contains few platelets and has reduced levels of factors V and VIII, although there are adequate amounts of the other coagulation factors. During massive transfusion (defined as transfusion of a volume of blood equal to the patient’s own blood volume within 24 hours, e.g. approximately 10 units in an adult), the platelet count and PT and PTTK should be checked at intervals. Transfusion of platelet concentrates and FFP should be considered if thrombocytopenia or defective coagulation are thought to be contributing to continued blood loss. Citrate binds ionized calcium and potentially lowers plasma calcium levels. This is rarely a problem as citrate is rapidly metabolized but neonates and hypothermic patients may have a reduced capacity for removal of citrate. Where there is clinical and ECG evidence of hypocalcaemia, 5 ml of 10% calcium gluconate should be given at 5 min intervals until the ECG is normal. The plasma potassium content of blood increases during storage but hyperkalaemia is rarely a problem unless very large volumes of blood are transfused rapidly.
Lactic acid is produced by red cell glycolysis in the blood pack and might contribute to the acidosis of hypoxic shocked patients. However, acidosis is usually improved by transfusion because of reversal of hypoxia and improved tissue perfusion.
Hypothermia may result from rapid transfusion of stored blood. Blood warmers should be used if the rate of infusion exceeds 1 unit in 10 min in adults and proportionately less in children.
Although it might be expected that massive transfusion of stored blood with high oxygen affinity due to low levels of 2,3-DPG would impair tissue oxygenation, there is little evidence that this occurs. Regeneration of 2,3-DPG is complete within a few hours following transfusion. The combination of hyperkalaemia, hypocalcaemia, hypothermia and acidosis might impair cardiac performance and even cause cardiac arrest. Careful monitoring of the patient’s temperature, plasma potassium and ECG for evidence of hypocalcaemia are essential in patients receiving rapid transfusions of large volumes of stored blood.
Inhibitors of coagulation In addition to the factor VIII:C alloantibodies that arise in up to 10% of severe haemophiliacs, factor VIII:C autoantibodies occasionally arise in patients with autoimmune disorders such as 5LE, in elderly patients and sometimes after childbirth. There may be severe bleeding. The antibodies may disappear spontaneously but treatment such as plasma exchange and immunosuppressive drugs may be required.
Lupus anticoagulants are IgG autoantibodies directed against phospholipids. They are found in about 10% of patients with 5LE and may also occur in otherwise healthy individuals. They lead to prolongation of phospholipiddependent coagulation tests, particularly the PTTK, but do not inhibit coagulation factor activity. Bleeding does  not occur unless there is coexistent severe immune thrombocytopenia. The main clinical problems are thrombosis, perhaps due to platelet activation due to inhibition of PGI2, and recurrent abortions.

Healthy Sex

Healthy Sex Assignment Help

People who have sex have higher quantity of safeguards for the body against germs, viruses, and other intruder.

People have to do all the other things which make their immune system joyful.

Remain active.

Stay educated about the vaccinations.

Always remember to use condoms, if people do not comprehend the STD statuses.

Fosters the Libido

Lauren Streicher says that having sex is likely to make sex better and certainly will boost the libido.
Highlighting the Bladder Control of Women; a strong pelvic ground is vital for preventing incontinence which can change within their own lives about 30% of girls sooner or later.
Great sex is the same as a exercise for the pelvic ground muscles. A culmination causes contractions in those muscles which augments the girls when they have got it.
Lauren Streicher is a medical director of CEO and Amai Wellness.

Pinzone says that sex is a truly exceptional form of exercise”.

A great sex life is good for the heart.

Decreases Pain

Strive for cumming before the reach for an aspirin.

It discharges a hormone which helps increase the pain threshold.

Stimulation without culmination could also work.

People do not want a partner to reap this advantage. Sexual intercourse nocturnal emission and masturbation have all portion of the equation.

Enriches Sleep

People may fall asleep off by rapidly following sex.

Relieves Stress

Sexual arousal discharges a brain substance that revs up the brain’s delight and reward system.
Ambardar says that the sex can increase the self-esteem and wellbeing. It is not simply a prescription for a healthy life, however a enjoyable one.

Healthy sexuality is more than having sex. It is about conveying, taking and giving fondness and love. It is the exercising of the sexual rights; and it is around discussing the feelings and values.
It is also a physical and mental desires, pleasure, gratification, self-image and esteem.
Sexuality is a part of human being.

People frequently learn about the values of physical well-being, mental health and religious well-being, however feeling assured about the sexual health is vital.

Healthy relationships

Planned pregnancies

Disorder prevention

It is essential to have the reason why it is vital to be well informed about all the facets of sexual health and a sex life. Similarly, it is crucial to understand about variables that might complicate the sexual health. Do not let embarrassment keep raise the problems or asking questions of the physician or other medical care providers.

The same as each physical task, healthy sex is good for the heart. Obviously, it helps the sex life and heart to stay fit.

Just looking at the partner (or merely a picture of the partner) can help alleviate pain. When anesthesiologists revealed people participating in a photos’ study of their close partners or pictures of attractive strangers or requested them to take part in a word game, they discovered that the encounter of pain dulled. Although, they may believe pain is a hurdle to sex. It is considered that sex can increase the worth of the time plus effort. Other studies have found that girls may get some relief through a great culmination from menstrual cramps.

Less pressure

Healthy sex provides the same soothing effects of comfort foods which are sugary in regards to reduce anxiety.

Cancer prevention

This would surely be a welcome sex gain while more research is required.

Better sleep

Specialists are unsure why the sex is helpful in order to enhance the sleep. It is satisfactory that if an individual and his partner take a short sleep after having sex.

Better temperament

It is no wonder that a person has a more favorable prognosis after sex: There are biochemical rationales for experiencing improved disposition from the neurotransmitters which will be published to the mood enhancers during healthy sex, as a sex gain within semen itself.

Radiant skin

People usually look better after having sex. That freshness could result from a combination of better predisposition, pressure alleviation, in addition to the flush of blood under the skin that is a portion of the arousal process. Adoring a healthy sex life is one of the exceptional happiness in life.

Coagulation disorders

Coagulation disorders may be inherited or acquired. The inherited disorders are uncommon and usually involve deficiency of one factor only. The acquired disorders occur more frequently and almost always involve several coagulation factors.



Deficiencies of all factors have been described. They are rare apart from haemophilia A (factor VIII deficiency), haemophilia B (factor IX deficiency) and von Willebrand’s disease.

Haemophilia A

In haemophilia A, the level of factor VIII:C is reduced but the level of factor VIII:vWF is normal. It is inherited as an X-linked recessive. The incidence of haemophilia A varies from 1 in 5000 to 1 in 10000 of the male population.
The human factor VIII gene was cloned in 1984. The gene is enormous, constituting about 0.1% of the X chromosome, encompassing 186 kilobases of DNA. Various genetic defects have been found, including deletions, point mutations and insertions. There is a high mutation rate with one-third of cases being apparently sporadic with no family history of haemophilia.


The clinical features depend on the level offactor VIII:C. Levels of less than 1% are associated with frequent spontaneous bleeding from early life. Haemarthroses are common and may lead to joint deformity and crippling if adequate treatment is not given. Bleeds into muscles are also common.
Levels of less than 5% are associated with severe bleeding, following injury and occasional spontaneous episodes, and levels above 5% with milder disease usually with post-traumatic bleeding only.
The most frequent cause of death in patients with severe haemophilia is AIDS. HIV was transmitted to many patients by coagulation factor concentrates in the 1980s.

Normal factor VIII synthesis

Normal factor VIII synthesis


The main laboratory features of haemophilia A are shown in Table 6.23. The abnormal findings are a prolonged PTTK and a reduced level offactor VIII:C; the PT, bleeding time and factor VIII :vWF level are normal.


Bleeding is treated by administration of factor VIII concentrate by intravenous injection. For minor bleeding the factor VIII level should be raised to 20-30% of normal, and for severe bleeding episodes it should be raised to at least 50%. For major surgery the level should be raised to 100% preoperatively and maintained above 50% until healing has occurred.

Blood changes in haemophilia A, von Willebrand's disease and vitamin K deficiency.

Blood changes in haemophilia A, von Willebrand’s
disease and vitamin K deficiency.

Factor VIII has a half-life of 12 hours and therefore must be administered twice daily to maintain the required therapeutic leveL Factor VIII concentrate may be stored in domestic refrigerators and so may be administered by the patient immediately after bleeding has started, reducing the likelihood of chronic damage to joints and the need for inpatient care. High purity factor VIII concentrates are now preferred to intermediate purity concentrates. Factor VIII:C produced by recombinant DNA technology is undergoing clinical trials.
DDAVP (i.v.) produces a rise in factor VIII proportional to the initial level of factor VIII. It avoids the complications associated with blood products and is useful for treating bleeding episodes in mild haemophiliacs and as prophylaxis before minor surgery.
All haemophiliacs should be registered at haemophilia centres, who take responsibility for their full medical care, including social and psychological support. Each haemophiliac carries a special medical card giving details of the defect and treatment.


About 10% of severe haemophiliacs develop antibodies to factor VIII:C. Inhibitors develop almost exclusively in patients with no detectable VIII:C. Management of such patients may be very difficult, and extremely high doses of factor VIII may be needed to produce a rise in the plasma level of factor VIII:C. Alternative treatment includes recombinant factor VIla, purified porcine factor VIII which may not cross-react with the patient’s antibody, and some factor IX concentrates containing activated factor X, which may ‘bypass’ the inhibitor and stop the bleeding. Following numerous transfusions there is a high risk of acquiring transfusion-transmitted infections, particularly hepatitis and HIV. The risk has been reduced by excluding high risk blood donors, testing all donations for HBsAg and HIV antibody, and by including steps to inactivate viruses during the preparation of concentrates. The use of recombinant factor VIII will avoid the risk of transfusion-transmitted infection; preliminary data suggest that it is safe and effective but there is a similar incidence of inhibitor development as with plasmaderived factor VIII. Carrier detection and antenatal diagnosis Determination of carrier status in females used to depend on detailed information from the family history and results of coagulation factor assays. Carriers could be diagnosed with reasonable confidence if the level of factor VIII:C was 50% of that expected from the level of factor VIII :vWF but often no clear-cut answer was provided by this method.
Carrier detection can now be carried out using DNA analysis either by direct detection of mutations within the factor VIII gene or by indirect detection of the abnormal gene using DNA polymorphisms within or adjacent to the factor VIII gene as markers of the abnormal gene. Antenatal diagnosis may be carried out by DNA analysis of fetal tissue obtained by chorionic villus biopsy at 9-11 weeks’ gestation or by using ultrasound-guided fetal blood sampling to detect low plasma levels in a fetus at 18-20 weeks of gestation.
Haemophilia B (Christmas disease) Haemophilia B is caused by a deficiency of factor IX. The inheritance and clinical features are identical to haemophilia A, but the incidence is only about 1:30 000 males. It is treated with factor IX concentrates.
von Willebrand’s disease (vWD) In vWD, there is defective platelet function as well as factor VIII:C deficiency and both are due to a deficiency or abnormality of factor VIII:vWF . Factor VIII:vWF plays a role in platelet adhesion to damaged subendothelium as well as stabilizing factor VIII:C in plasma.
The VIII:vWF gene is on chromosome 12 and numerous mutations of the gene have been identified. vWD has been classified into three types: TYPE I is characterized by a mild reduction in factor VIII :vWF and is inherited as an autosomal dominant.
TYPE II is due to a decrease in the proportion of high molecular weight multimers and is also inherited as an autosomal dominant.
TYPE III is recessively inherited and patients have barely detectable levels of factor VIII:vWF (and therefore factor VIII:C).
The clinical features of vWD are variable. Type I and type II patients usually have mild clinical features. Bleeding follows minor trauma or surgery and epistaxis and menorrhagia often occur. Haemarthroses are rare. Type III patients have clinical features resembling haemophilia A. Characteristic laboratory findings are shown . These also include defective platelet aggregation with ristocetin.
Treatment depends on the severity of the condition and may be similar to that of mild haemophilia, including the use of DDAVP for minor surgery. Factor VIII concentrates should be used to treat bleeding or to cover surgery in patients with severe vWD. Cryoprecipitate should be avoided because of the greater risk of transfusiontransmitted infection.

Platelet disorders

Bleeding due to thrombocytopenia or abnormal platelet function is characterized by purpura and bleeding from mucous membranes. Bleeding is uncommon with platelet counts above 50 X 109/litre, and severe spontaneous bleeding is unusual with platelet counts above 20 X 109/litre.


This is caused by reduced platelet production in the bone marrow or excessive peripheral destruction of platelets. A bone marrow aspirate to assess whether the numbers of megakaryocytes are reduced or normal/increased is an essential part of the investigation.

Causes of thrombocytopenia.

Causes of thrombocytopenia.

Autoimmune thrombocytopenic purpura (AITP)

Thrombocytopenia is due to immune destruction of platelets. The sensitized platelets are removed by the reticuloendothelial system. There are two distinct clinical syndromes.
Acute AITP is usually seen in children, often following a viral infection. It has been suggested that the thrombocytopenia is due to the deposition of immune complexes on platelets, but the acute development of platelet autoantibodies is probably responsible for the shortened platelet survival.
Chronic AITP is characteristically seen in adult women. It is usually idiopathic but may occur in association with other autoimmune disorders such as SLE, thyroid disease and autoimmune haemolytic anaemia (Evans’ syndrome), in patients with chronic lymphocytic leukaemia and solid tumours and after viral infections with viruses such as HIV. Platelet autoantibodies are detected in about 60-70% of patients, and are presumed to be present, although not detectable, in the remaining patients.


Major haemorrhage is rare and is only seen in patients with severe thrombocytopenia. Easy bruising, purpura, epistaxis and menorrhagia are common. Physical examination is normal except for evidence of bleeding. Splenomegaly is rare.


The only blood count abnormality is thrombocytopenia. Normal or increased numbers of megakaryocytes are found in the bone marrow, which is otherwise normal. The detection of platelet autoantibodies is not essential for confirmation of the diagnosis, which often depends on exclusion of other causes of excessive destruction of platelets.


Acute AITP in children usually remits spontaneously. It is still not clear whether treatment in the acute phase with steroids or high-dose intravenous immunoglobulin is effective in minimizing the period of thrombocytopenia or in reducing the incidence of chronic AITP, which develops in 5-10% of children.
Spontaneous remissions are rare in chronic AITP. The main aims of treatment are to reduce the production of platelet autoantibodies and the removal of antibodycoated platelets. Initial treatment is with prednisolone, 40-60 mg daily in adults with cautious reduction of the dose after remission has occurred.
Twenty per cent of patients have a complete response and require no further treatment; 60% have a partial response, and half of these have little bleeding associated with mild or moderate thrombocytopenia (platelet count 30-100 X 1Q9/litre) and may require small doses of steroids, such as prednisolone 5-15 mg daily, or no further treatment. The other half of the partial responders eventually relapse and require splenectomy, as do the 20% of patients who failed to respond to steroids at all. Splenectomy should be avoided in young children because of the subsequent risk of severe pneumococcal infection. There is a 90% response rate to splenectomy, although about 30% of responders eventually relapse. Some of these refractory patients may respond to immunosuppressive drugs such as azathioprine, cyclophosphamide or vincristine or to danazol, which is a non-virilizing androgen. Intravenous infusion of high-dose immunoglobulin produces a rapid rise in the platelet count due to blockade of Fe receptors in the spleen. The increase in platelet count is usually transient but may be useful in patients with acute haemorrhage and in preparing patients with chronic AITP for surgery. Transfused platelets survive no longer than the patient’s own platelets but may sometimes be beneficial in patients with life-threatening bleeding. Other immune thrombocytopenias
DRUGS cause immune thrombocytopenia by the same mechanisms as described for drug-induced immune haemolytic anaemia. The same drugs may be responsible for immune haemolytic anaemia, thrombocytopenia or neutropenia in different patients; it is not known what determines the target cell in each case.
FETOMATERNAL ALLOIMMUNE THROMBOCYTOPENIA is due to fetomatemal incompatibility for plateletspecific antigens, usually for HPA-1a (human platelet alloantigen, previously called PIAl), and is the platelet equivalent of HDN. The mother is HPA-1a-negative and produces antibodies which destroy the HPA-1a-positive  fetal platelets.
Thrombocytopenia is self-limiting after delivery, but platelet transfusions may be required to prevent or treat bleeding associated with severe thrombocytopenia; platelets may be prepared from HPA-1a-negative volunteers or the mother herself. Recently, it has been recognized that severe bleeding such as intracranial haemorrhage may occur in utero. Antenatal treatment of the mother with steroids and/or high-dose intravenous immunoglobulin or platelet transfusions given directly to the fetus by ultrasound-guided needling of the umbilical vessels have been effective in preventing haemorrhage in severely affected cases.
POST-TRANSFUSION PURPURA (PTP) is rare, occurring 2-12 days after a blood transfusion. PTP is associated with a platelet -specific alloantibody, usually anti- HPA-Ia in a HPA-1a-negative individual. PTP almost invariably occurs in females who have been previously immunized by pregnancy or blood transfusion. The cause of the platelet destruction is uncertain. PTP is self-limiting but high-dose intravenous immunoglobulin may limit the period of thrombocytopenia.


These are usually asociated with excessive bruising and bleeding and, in some of the acquired forms, with thrombosis. The platelet count is normal or increased and the bleeding time is prolonged. The rare inherited defects of platelet function require more detailed investigations such 3S platelet aggregation studies and factor VIII:C and VIII :vWF assays, if von Willebrand’s disease is suspected. Acquired forms of platelet dysfunction include:
• Myeloproliferative disorders
• Uraemia and liver disease
• Paraproteinaemias
• Drugs, e.g. aspirin and dipyridamole
If there is serious bleeding or if the patient is about to undergo surgery, drugs with antiplatelet activity should be withdrawn and any underlying condition should be corrected if possible. In patients with renal failure, the haematocrit should be increased to greater than 0.30 litre litre'” and the use of desmopressin (DDAVP) may be helpful. Platelet transfusions may be required if these measures are unsuccessful.

Vascular disorders

The vascular disorders , sometimes previously classified as non-thrombocytopenic purpuras, are characterized by easy bruising and bleeding into the skin. Bleeding from mucous membranes sometimes occurs but the bleeding is rarely severe. Laboratory investigations including the bleeding time are normal. The vascular disorders include the following.

Vascular disorders.

Vascular disorders.

This is a rare disorder with autosomal dominant inheritance. Dilatation of capillaries and small arterioles produces characteristic small red spots that blanch on pressure in the skin and mucous membranes, particularly the nose and gastrointestinal tract. Recurrent epistaxis and chronic gastrointestinal bleeding are the major problems and may cause chronic iron deficiency anaemia.
EASY BRUISING SYNDROME. This is a benign disorder occurring in otherwise healthy women. It is characterized by bruises on the arms, legs and trunk with minor trauma, possibly due to skin vessel fragility. It may give rise to the suspicion of a serious bleeding disorder.SENILE PURPURA AND PURPURA DUE TO STEROIDS.

These are both due to atrophy of the vascular supporting tissue.
PURPURA DUE TO INFECTIONS. This is mainly due to damage to the vascular endothelium.
HENOCH-SCHONLEIN PURPURA. This usually occurs in children. It is a type III hypersensitivity reaction that is often preceded by an acute upper respiratory tract infection. Purpura is mainly seen on the legs and buttocks. Abdominal pain, arthritis, haematuria and nephritis also occur. Recovery is usually spontaneous but some patients develop renal failure.
FACTITIAL PURPURA. Episodes of inexplicable bleeding or bruising may represent abuse, either self-inflicted or caused by others. These various forms of artificial or factitious purpuras are often expressions of severe emotional or psychiatric disturbances.

Investigation of bleeding disorders

Although the  precise diagnosis of a bleeding disorder may depend on laboratory tests, much information may be obtained from  the history and physical examination, which should   aim to determine the following:
1 Is there ageneralized haemostatic defect? Supportive evidence for this includes bleeding from multiple sites, spontaneous bleeding and bleeding into the skin. 2 Is the feet inherited or acquired? A family history of a a bleeding disorder should be sought. Severe inherited defects usually become apparent in infancy, while mild inherited defects may only come to attention later in life, for example with excessive bleeding after surgery, childbirth, dental extractions or trauma.

3 Is the bleeding suggestive of a vascular/platelet defect or a coagulation defect?
VASCULAR/PLATELET BLEEDING is characterized by easy bruising and spontaneous bleeding from small vessels. The bleeding is mainly into the skin (the term purpura includes both petechiae, which are small skin haemorrhages varying from pinpoint size to a few millirnetres in diameter and which do not blanch on pressure, and ecchymoses, which are small bruises) and from mucous membranes, often from the nose and mouth.
COAGULATION DISORDERS are typically associated with haem arthroses and muscle haematomas.


BLOOD COUNT AND FILM show the number and morphology of platelets and any blood disorder such as leukaemia.
BLEEDING TIME measures platelet plug formation in vivo. It is determined by applying a sphygmoman ometer cuff to the arm and inflating it to 40 mmHg.
Two 1 mm deep, 1 cm long incisions are made in the forearm with a template. Each wound is blotted every 30 s and the time taken for bleeding to stop is recorded, normally between 3 and 10 min. Prolonged bleeding times are found in patients with platelet function defects and there is a progressive prolongation with platelet counts less than 80 X 109/litre. The Hess or capillary resistance test parallels the bleeding time but is unreliable and not routinely used.



COAGULATION TESTS are performed using blood collected into citrate, which neutralizes calcium ions and prevents clotting. The prothrombin time (PT) is measured by adding tissue thromboplastin in the form of animal brain extract and calcium to patient’s plasma. The normal PT is 16-18 s and it is prolonged with abnormalities of either the extrinsic or common pathways. The partial thromboplastin time with kaolin (PTTK) is also known as the APTT (activated PTT). It is performed by adding a surface activator, kaolin, phospholipid (as platelet substitute) and calcium to patients’ plasma. The normal PTTK is 30-50 s depending on the exact methodology, and it is prolonged with abnormalities of either the intrinsic or common pathways. The thrombin time (TT) is performed by adding thrombin to patients’ plasma. The normal TT is about 12 s, and it is prolonged with fibrinogen deficiency, dysfibrinogenaemia (normal level of fibrinogen but abnormal function) or inhibitors such as heparin or FDPs. Correction tests are used to differentiate prolonged times in the PT, PTTK and TT due to coagulation factor deficiencies and inhibitors of coagulation. Prolonged PT, PTTK or TT due to coagulation factor deficiencies are corrected by addition of normal plasma to the patient’s plasma; no correction of an abnormal result after the addition of normal plasma is suggestive of the presence of an inhibitor of coagulation. Special tests of coagulation will often be required to confirm the precise haemostatic defect. Such tests include estimation of fibrinogen and FDPs, assays of coagulation factors, platelet function tests such as platelet aggregation and tests of the fibrinolytic pathway which include the euglobulin clot lysis time (ELT) and assays of plasminogen, t-PA and PAl-I. The ELT involves precipitation by acidification of the euglobulin fraction of plasma which contains fibrinogen, plasminogen and plasminogen activators. The euglobulin is clotted with thrombin and the time taken for lysis of the fibrin clot is a measure of fibrinolytic activity; the normal range is 60-270 min.

Bleeding disorders

Blood is normally separated from the activators of haemostasis by the endothelial cell. Injury to the vessel wall exposes collagen and sets in motion a series of events leading to haemostasis.


Haemostasis is a complex process depending on interactions between the vessel wall, platelets and coagulation factors.

Vessel wall

An immediate reflex vasoconstriction of the injured vessel and adjacent vessels results in a transient reduction of blood flow to the affected area. Damage to the endothelium of the vessel results in activation of platelets and coagulation; release of serotonin and thromboxane A2 (TXA2) from activated platelets contributes to the vasoconstriction.


Platelet adhesion to collagen is dependent on platelet membrane receptors, glycoprotein Ia (GPIa), which binds directly to collagen, and glycoprotein Ib (GPIb), which binds to von Willebrand factor (VIII:vWF) in the plasma and VIII :vWF in turn adheres to collagen. Following adhesion, platelets undergo a shape change from a disc to a sphere, spread along the subendothelium and release the contents of their cytoplasmic granules, i.e. the dense bodies (containing ADP and serotonin) and the ex-granules (containing platelet-derived growth factor, platelet factor 4, l3-thromboglobulin, fibrinogen, VIII:vWF and other factors).
The release of ADP leads to exposure of a fibrinogen receptor, the glycoprotein IIb-IIIa complex (GPIIb-IIIa), on surfaces of adherent platelets; fibrinogen binds platelets into activated aggregates (platelet aggregation) and further platelet release occurs. A self-perpetuating cycle of events is set up leading to formation of a platelet plug at the site of the injury.
Further platelet membrane receptors are exposed during aggregation, providing a surface for the interaction of coagulation factors; this platelet activity is referred to as platelet factor 3 (PF-3). The presence of thrombin encourages fusion of platelets, and fibrin formation reinforces the stability of the platelet plug. Central to normal platelet function is platelet prostaglandin synthesis, which is induced by platelet activation and leads to the formation of TXA2 in platelets. TXA2 is a powerful vasoconstrictor and also lowers cyclic AMP levels and initiates the platelet release reaction.
Prostacyclin (PGI2) is synthesized in vascular endothelial cells and opposes the actions of TXA2. It produces vasodilatation and increases the level of cyclic AMP, preventing platelet aggregration on the normal vessel wall as well as limiting the extent of the initial platelet plug after injury.

Coagulation and fibrinolysis

Coagulation involves a series of enzymatic reactions leading to the conversion of soluble plasma fibrinogen to fibrin clot (Fig. 6.26). The coagulation factors are either enzyme precursors (factors XII, XI, X, IX and thrombin) or cofactors (V and VIII), except for fibrinogen, which is the subunit of fibrin. The enzymes apart from factor XIII are serine pro teases and hydrolyse peptide bonds.
EXTRINSIC PATHWAY. Coagulation is initiated by tissue factor, which is expressed on the surface of perivascular tissue cells, coming into contact with plasma after an injury. The complex of activated factor VII and tissue factor activates factor X but its main role in vivo is to activate factor IX in the intrinsic pathway.
INTRINSIC PATHWAY. Factor XII was thought to be activated by ‘contact’ with the injured surface and then to initiate a series of reactions beginning with activation of factor XI and leading to activation of factor X. The upper part of the intrinsic pathway includes kallikrein and high molecular weight kininogen (HMWK) but recent evidence suggests that this part of the intrinsic pathway is not important for in vivo haemostasis. It is now thought that factor IX is activated by a complex of tissue factor and factor VII. Activated factor IX together with factor VIII and calcium ions activate factor X. Factor XI is activated in vivo by thrombin and only maIces an important contribution after major trauma.
Factor VIII is a complex protein consisting of a small molecule with coagulant activity (VIII:C) and a larger part, von Willebrand factor (VIII :vWF) , which is associated with platelet adhesion. VIII:C is a single chain protein with a molecular weight of about 350000. VIII :vWF a glycoprotein with a molecular weight of about 200000. It readily forms multimers in the circulation with molecular weights of up to 20 X 106. The high molecular weight multimeric forms of VIII :vWF are the most effective  in producing platelet adhesion.

COMMON PA THWA Y. Activated factor X eventually leads to the conversion of prothrombin to thrombin. Thromhydrolyses bin the peptide bonds of fibrinogen, releasing fabrinopeptides A and B, and allowing polymerization between fibrinogen molecules to form fibrin. At the same time thrombin, in the presence of calcium ions, activates factor XIII, which stabilizes the fibrin clot by cross-linking adjacent fibrin molecules. The presence of thrombin helps in the activation of factors XI, V, VIII and XIII.

LIMITATION OF COAGULATION. Coagulation is limited to the site of injury by removal of activated coagulation factors by rapid blood flow at the periphery of the damage area,  by plasma inhibitors of activated coagulation factors and by fibrinolysis.
Antithrombin III (AT-III) is the most potent inhibitor of coagulation; it inactivates the serine proteases by foreming stable complexes with them and its action is greatly protentiated by heparin. Active protein C is generated from its vitamin K-dependent precursor by the action of thrombin; thrombin activation of protein C is enhanced  when thrombin is bound to thrombomodulin, which is an endothelial cell receptor (Fig. 6.27). Active protein C destroys factor V and factor VIII reducing further thrombin generation. Protein S is a cofactor for protein C by allowing binding of activated protein C to the platelet surface. Other natural inhibitors of coagulation are 0’2- macroglobulin, O’J-antitrypsin, O’J-antiplasmin and heparin cofactor II.

Formation of the haemostatic plug. Sequential interactions of the vessel wall, platelets and coagulation factors.

Formation of the haemostatic plug. Sequential interactions of the vessel wall, platelets and coagulation factors.

Prostaglandin synthesis (simplified).

Prostaglandin synthesis (simplified).

Coagulation sequence.

Coagulation sequence.

FIBRINOLYSIS, which helps to restore vessel patency, also occurs in response to vascular damage. In this system (Fig. 6.28), an inactive plasma protein, plasminogen, is converted to plasmin by plasminogen activators derived from the plasma or blood cells (intrinsic activation) or the tissues (extrinsic activation).

Plasmin is a serine protease which breaks down fibrinogen and fibrin into fragments X, Y, D and E, collectively known as fibrin (and fibrinogen) degradation products (FDPs). Degradation of cross-linked fibrin also yields D-dimer and D-dimer-E fragments. Plasmin is also capable of breaking down coagulation factors such as factors V and VIII.
The fibrinolytic system is activated by the presence of fibrin. Plasminogen is specifically adsorbed to fibrin and fibrinogen by lysine-binding sites. However, little plasminogen activation occurs in the absence of fibrin, as fibrin also has a specific binding site for plasminogen activators, whereas fibrinogen.

Activation of protein C. PAI-1, plasminogen activator inhibitor

Activation of protein C. PAI-1, plasminogen activator inhibitor

Fibrinolytic system.

Fibrinolytic system.

The most important plasminogen activator is tissuetype plasminogen
activator (t-PA); vascular endothelium is the major source of t-PA in plasma. Its release is stimulated by  thrombin. Another plasminogen activator is urokinase synthesized in the kidney and released into the urogenital tract. Intrinsic plasminogen activators such as factor XlI and kallikrein are of minor physiological importance.

T- PA is inactivated by plasminogen activator inhibitor 1 . Activated protein C inactivates PAl – I and therefore induces fibrinolysis. Inactivators of plasmin (such as a2-antiplasmin) are also present in the and contribute to the regulation of fibrinolysis.