Acquired coagulation disorders
Acquired coagulation disorders are more common than inherited disorders, with various causes such as vitamin K deficiency, liver disease, and inhibitors affecting clotting factors. Vitamin K deficiency can be seen in children and adults due to multiple factors, leading to a decrease in functional activity of clotting factors. Hemorrhagic disease of the newborn, liver disease, and other conditions contribute to bleeding tendencies and abnormal clotting. Understanding the mechanisms and risk factors associated with acquired coagulation disorders is essential for proper management.
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Acquired coagulation disorders Professor Abeer Anwer Ahmed
Acquired coagulation disorders: They are more common than the inherited disorders. Unlike the inherited disorders, multiple clotting factor deficiencies are usual.
The acquired coagulation disorders. Deficiency of vitamin K-dependant factors Haemorrhagic disease of the newborn Biliary obstruction Malabsorption of vitamin K(e.g. tropical sprue, gluten induced enteropathy) Vitamin K-antagonist therapy (e.g. coumarins, indandiones) Liver disease Disseminated intravascular coagulation Inhibition of coagtulation Specific inhibitors (e.g. antibodies against factor VIII) Non-specific inhibitors (e.g. antibodies found in systemic lupus erythematosus, rheumatoid arthritis) Miscellalleous Diseases with M-protein production L-Asparaginase Therapy with heparin, defibrinating agents or thrombolytics Massive transfusion syndrome
Vitamin K deficiency in children or adults Caused by : obstructive jaundice pancreatic small bowel disease inadequate diet malabsorption drugs as warfarin which act as vit.K antagonists is associated with decrease in functional activity of factors : II, VII,IX, X & protein C & S ,but the immunological methods show normal levels of these factors.
Haemorrhagic disease of the newborn Vitamin K-dependent factors are low at birth and fall further in breast-fed infants in the first few days of life. Liver cell immaturity, lack of gut bacterial synthesis of the vitamin and low quantities in breast milk may all contribute to a deficiency which may cause haemorrhage, usually on the second to fourth day of life, but occasionally during the first 2 months
liver disease Multiple haemostatic abnormalities contribute to a bleeding tendency and may exacerbate haemorrhage from oesophageal varices, 1 Biliary obstruction results in impaired absorption of vitamin K and therefore decreased synthesis of factors II, VII, IX and X. 2 With severe hepatocellular disease, in addition to a deficiency of these factors, there are often reduced levels of factor V and fibrinogen and increased amounts of plasminogen activator
3 Functional abnormality of fibrinogen (dysfibrinogenaemia) 4 Decreased thrombopoietin production from the liver contributes to thrombocytopenia. 5 Hypersplenism associated with portal hypertension frequently results in thrombocytopenia. 6 Disseminated intravascular coagulation
Massive transfusion syndrome Many factors may contribute to a bleeding disorder following massive transfusion, Blood loss results in reduced levels of platelets, coagulation factors and inhibitors, Further dilution of these factors occurs during replacement with red cells,
Haemostasis tests in Acquired coagulation disorders
Thrombi are solid masses or plugs formed in the circulation from blood constituents. Platelets and fibrin form the basic structure. Their clinical significance results from ischaemia from local vascular Obstruction or distant embolization.
Hereditary disorders of haemostasis A hereditary thrombophilia' should be particularly suspected in *young patients who suffer from spontaneous thrombosis, *recurrent deep vein thromboses *an unusual site of thrombosis (e.g. axillary, splanchnic veins, sagittal sinus). :
Factor V Leiden gene mutation (activated protein C resistance) This is the most common inherited cause of an increased risk of venous thrombosis. It occurs in approximately 4% of Caucasian factor V alleles Patients who are heterozygous for factor V Leiden are at an approximately 5-8-fold increased risk of thrombosis compared to the general population. Individuals who are homozygous have a 30-140 fold risk. Following venous thrombosis they have a higher risk of re- thrombosis compared to individuals with deep vein thrombosis (DVT) but normal factor V.
the underlying reason a genetic polymorphism in the factor V gene (replacement of arginine at position 506 with glutamine-Arg506Gln) which makes factor V less susceptible to cleavage by activated protein C * screening :polymerase chain reaction (PCR) screening for the mutation is relatively simple and the test is widely performed.
Anti-thrombin deficiency Inheritance is autosomal dominant. There are recurrent venous thromboses usually starting in early adult life. Arterial thrombi occur occasionally. Anti-thrombin concentrates are available and are used to prevent thrombosis during surgery or childbirth.
Protein C deficiency Inheritance is autosomal dominant with variable Protein C levels in heterozygotes are approximately 50% of normal. Characteristically, many patients develop skin necrosis as a result of dermal vessel occlusion when treated with warfarin, Rarely, infants may be born with homozygous deficiency and characteristically present with severe disseminated intravascular coagulation (DIC) or purpura fulminans in infancy.
Protein S deficiency The inheritance is autosomal dominant. found in a number of families with a thrombotic tendency. It is a cofactor for protein C and the clinical features are similar to protein C deficiency, including a tendency to skin necrosis with warfarin therapy.
Prothrombin allele G20210A Prothrombin allele G20210A is a variant (prevalence2-3% in the population) that leads to increased plasma prothrombin levels and increases thrombotic risk by at least twofold
Hyperhomocysteinaemia homocystinuria is a rare autosomal recessive disorder Higher levels of plasma homocysteine may be genetic or acquired and are associated with increased risk for both venous and arterial thrombosis. Vascular disease and thrombosis are major features of the disease. Heterozygous present in approximately 0.5% of the population and leads to a moderate increase in homocysteine.
Acquired risk factors for hyperhomocysteinaemia Include: deficiencies of folate, vitamin BI2 or vitamin B6 drugs (e.g. ciclosporin) renal damage and smoking. The levels also increase with age and are higher in men and post-menopausal females
Hereditary or acquired disorders of haemostasis High factor VIII or fibrinogen levels are also associated arterial thrombosis. The combination of multiple risk factors is associated with increased risk of thrombosis.
Acquired risk factors Postoperative venous thrombosis This is more likely to occur in the elderly, obese, those with a previous or family history of venous thrombosis, and in those in whom major abdominal or hip operations are performed Venous stasis and immobility These factors are probably responsible for the high incidence of postoperative venous thrombosis and for venous thrombosis associated with congestive cardiac failure, myocardial infarction and varicose veins
Malignancy Patients with carcinoma of the ovary, brain and pancreas have a particularly increased risk of venous thrombosis but there is an increased risk with all cancers. The tumours produce : tissue factor and a pro-coagulant that directly activates factor X. Mucin-secreting adenocarcinomas may be associated with DIC.
Inflammation This up-regulates procoagulant factors, down regulates anticoagulant pathways, particularly protein C. Thrombosis is particularly likely in inflammatory bowel disease, Behcet's disease, systemic tuberculosis, systemic lupus erythematosus :
Blood disorders *in patients with polycythaemia vera and essential thrombocythaemia, the high incidence of thrombosis is due to : -Increased viscosity, -Thrombocytosis, -altered platelet membrane receptors and responses *There is a high incidence of venous thrombosis in patients with sickle cell disease and patients *with post splenectomy thrombocytosis
Oestrogen therapy Oestrogen therapy, particularly high-dose therapy, is associated with: * increased plasma levels of factors II, VII, VIII, IX and X and *depressed levels of antithrombin and tissue plasminogen activator in the vessel wall. There is a high incidence of postoperative venous thrombosis in women on high-dose oestrogen therapy and full-dose oestrogen-containing oral contraceptives.
The antiphospholipid syndrome This may be defined as the occurrence of thrombosis or recurrent miscarriage in association with laboratory evidence of persistent antiphospholipid antibody. *One antiphospholipid antibody is the 'lupus anticoagulant' (LA) which was initially detected in patients with SLE *and also found in other autoimmune disorders particularly of connective tissues * lymphoproliferative diseases *post-viral infections with certain drugs including phenothiazines *and as an 'idiopathic' phenomenon in otherwise healthy subjects. it is associated with venous and arterial thrombosis.
Factor IX concentrates Venous thrombosis may complicate the use of factor IX concentrates which contain trace amounts of activated coagulation factors. Patients with liver disease who are unable to clear these activated factors are especially at risk.
