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.

Posted by: brianna


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