|Cerebral Venous Sinus thrombosis
|Protein C Deficiency
|Protein S Deficiency
|Antithrombin III deficiency (AT3)
- Two internal systems exist - one to encourage clot formation another to discourage clot formation
- Pro thrombotic disorders exist when there is excess thrombus formation
- These disorders can be congenital or acquired
- Thrombosis starts when one starts combining risks e.g. HRT/OCP and prothrombotic disorder and a smoker
Clinical Indications for screening
- Patients under 40 with unexplained VTE
- Family history of VTE in relative less than 40
- Venous thrombosis with no obvious precipitating cause or at a relatively young age. Presently this is advised below the age of 50.
- Women with a history of recurrent miscarriages should be screened for the lupus anticoagulant
- Under 60 years with VTE in unusual site e.g. cerebral venous sinus thrombosis, portal vein thrombosis, mesenteric, subclavian.
- Arterial thrombosis (Stroke/Definite TIA) where there is no other obvious cause in those under 40: anticardiolipin and lupus anticoagulant
Pro thrombotic states
- Factor V Leiden mutation: A mutation of one of the clotting factors is seen in 5% of the normal population. The mutation makes it less vulnerable to breakdown by Protein C and so increased factor V activity and clots
- Prothrombin 20210A gene mutation : seen in 2 %. There is elevated prothrombin levels and a 3 times increase risk of thrombosis
- Protein C or S deficiency: Skin necrosis with Warfarin. Protein C cleaves factor V and so reducing clotting. Its deficiency therefore increases clotting.
- Antithrombin III deficiency: Heterozygous x 4 risk of VTE Homo - No survival. Those with Antithrombin III deficiency are relatively resistant to Heparin as Heparin usually acts via its effect on ATIII. Can also be acquired after trauma or surgery, pregnancy and nephrotic syndrome
- Pregnancy and Oral contraceptive usage
- Paroxysmal nocturnal haemoglobinuria (PNH)
- Polycythemia vera and essential thrombocythemia: elevated erythrocyte mass or platelet count, splenomegaly, and bone marrow hypercellularity. The risk of thrombosis is highest in patients over the age of 60 and in those with a previous history of thrombosis
- Hyperhomocysteinemia - Increased risk of arterial thrombosis and MI or stroke. Treat with Folate, B6 and B12
- Heparin-induced thrombocytopenia (HIT)
- Malignancies: migratory superficial thrombophlebitis (Trousseau syndrome), VTE, DIC, or ischemic stroke. Trousseau syndrome and VTE usually associated with carcinomas of the pancreas, lung, prostate, breast, uterus, stomach, and colon. DIC with adenocarcinomas or acute leukaemias. Cardioembolic stroke in cancer patients often arises from nonbacterial thrombotic endocarditis.
- Antiphospholipid syndrome is an acquired disorder in which vascular thrombosis and complications of pregnancy are associated with autoantibodies directed toward phospholipids or phospholipid-binding proteins.
- FBC (platelets)
- Coagulation screen with fibrinogen level
- Thrombophilia screening should not be done during the acute phase after the patient presents with a clot. Patients should be tested after the acute event and after any anticoagulation therapy (1-month post Warfarin therapy).
Thrombophilia screen in Venous thrombosis or Paradoxical embolism
- Look for low Antithrombin, Protein C levels, Protein S levels
- Prothrombin 20210A and Factor V Leiden looking for gene mutation
- Lupus anticoagulant, Anticardiolipin antibodies
- Plasma total homocysteine
Thrombophilia screen in Arterial thrombosis
- Lupus anticoagulant, Anticardiolipin antibodies, Plasma total homocysteine
- If under 50 check Factor V Leiden, Prothrombin 20210A, Antithrombin, Protein C, Protein S
Sample requirements: 2 * 3.2mL citrate (blue-capped) tube, 5mls of blood in EDTA (lilac capped) tubes, 1 * EDTA sample tube (lilac-capped), 1 * Clotted sample tube no anticoagulant (mustard-capped). NB Citrate sample tubes must be filled to the correct level.
- Anti-thrombin 0.8-1.2 IU/ml : Not reliable in patients receiving Heparin or low-molecular weight Heparin.
- Protein C 0.7-1.4 IU/ml: Not reliable in patients receiving Warfarin or in the acute period following a thrombotic event
- Protein S total 0.7-1. IU/mL: Not reliable in patients receiving Warfarin or in the acute period following a thrombotic event
- APC resistance ratio Ratios of greater than 2.5
- Factor V Leiden - reported as normal, abnormal (heterozygous) or abnormal (homozygous)
- Prothrombin gene mutation reported as normal, abnormal (heterozygous) or abnormal (homozygous)
- Lupus anticoagulant - depends upon an analysis of a series of clotting assays and would always be reported in an interpretive manner
- Anticardiolipin antibodies: Standardized immunoassays for immunoglobulin G or immuno- globulin M antibodies that recognize bovine cardiolipin in a molecular complex with alpha 2-glycoprotein I.