LT.05 Management of Thrombosis (Including Prophylaxis) PDF

LT.05. Management of Thrombosis (Including Prophylaxis) Aim To study the management and prophylaxis of thrombosis. Objective Describe the principals involved in the management and prophylaxis of thrombosis. Treatment Once a DVT has been diagnosed, anticoagulation is started but treatment of small...

LT.05. Management of Thrombosis (Including Prophylaxis) Aim To study the management and prophylaxis of thrombosis. Objective Describe the principals involved in the management and prophylaxis of thrombosis. Treatment Once a DVT has been diagnosed, anticoagulation is started but treatment of small thromboses below the knee is controversial: some experts believe that no initial treatment is needed for these small thrombi and that monitoring with e.g. repeat Doppler examination looking for extension to the knee and beyond prior to treatment, is all that is needed. All major thromboses above the knee should however be treated. The initial treatment is heparin (unfractionated (UFH) or low molecular weight heparin (LMWH)) or a Direct Oral Anticoagulant (DOAC) e.g. rivaroxaban. Heparin, a mucopolysaccharide, enhances the proteolytic action of antithrombin on coagulation factors Xa and IIa. LMWH is not as strongly plasma protein bound as UFH and acts mostly on FXa but also acts via augmentation of antithrombin. Heparins do not lyse clots but inhibit clot extension providing an opportunity for the body’s own fibrinolytic system to lyse the clot. o UFH: action of ~2 hours; given subcutaneously or intravenously; activity is monitored with the activated partial thromboplastin time (aPTT). The target is to increase the aPTT 2-2.5 times the patient’s normal or the control aPTT. The dose of UFH is adjusted according to the aPTT result. The aPTT is done 12 hrly and the sample must reach the laboratory within 2-hours of the phlebotomy. o LMWH: action of ~12 hours; has largely replaced UFH; given subcutaneously; activity is monitored with an anti-Factor Xa level but it is not mandatory owing to the predictable action of LMWH and is only needed in certain patients i.e. obese, pregnant, renal dysfunction, elderly and children. DOACs act directly on either activated FIIa or Xa without an intermediate molecule such as antithrombin. These agents are no used both during the acute phase of treatment of venous thromboses as well as for ongoing therapy owing to their efficacy, predictable anticoagulant effect (activity monitoring is therefore not routinely needed) as well as ease of administration. Rivaroxaban is currently available at CMJAH and the details below are from the anticoagulation clinic standard operating procedure: INDICATIONS FOR DOAC DOSE AND DURATION Prevention of stroke and systemic embolism Rivaroxaban (ixarola) 20 mg OD in patients in non-valvular atrial fibrillation* with eGFR > 50 mL/min lifelong** Acute treatment of DVT and PE Rivaroxaban (ixarola) 15mg BD or Clexane 1mg/kg bd sc for the intial 3 weeks followed by Rivaroxaban (ixarola) 20 mg OD after 3 weeks for at least 3 months with eGFR > 50 mL/min** Continued prevention of recurrent DVT and For extended therapy beyond 6 months, PE Rivaroxaban (ixarola) 20 mg OD  Rivaroxaban (ixarola) 10 mg OD in select patients requiring extended therapy. Registered indications include: Nonsurgical provoked VTE First unprovoked VTE *Excludes patients with rheumatic heart disease or mechanical heart valves **eGFR 30-49 mL/min a dose reduction of 15mg OD is recommended or anti-Xa monitoring. ** GFR< 30 mL/min, in accordance with the ESC guidelines rivaroxaban is not recommended. Please note the ixarola on code is a 10mg, 15mg and 20mg tablet which is not scored. Fibrinolytic agents e.g. streptokinase administered systematically or locally (via a catheter to the site of the clot) lyses thromboses but currently there is not enough data to support their routine use for DVTs except in venous gangrene of the leg. The major side effect of anticoagulation is bleeding which can be avoided to a large extent by monitoring anticoagulant activity since bleeding increases with over-anticoagulation. Heparin-induced thrombocytopenia (HIT) is a side effect of heparin therapy. HIT is an auto-immune disease Platelet levels drop after starting heparin: more common with UFH Sudden increase in the amount of heparin required to maintain an adequate aPTT Associated paradoxically with thrombosis Must check platelet count at least weekly in patients on heparin Patients on long-term heparin (e.g. pregnant women on prophylaxis) have a low risk of HIT after a month and therefore it is not mandatory to check platelet counts in these patients Most heparin treatment regimens for venous thrombosis are for 7-10 days of either intravenous UFH or subcutaneous LMHW. The patients are generally started on Day 1 or 2 on warfarin therapy. Warfarin is a vitamin K epoxide reductase inhibitor and causes a relative vitamin K deficiency. Vitamin K is essential for γ carboxylation of factors II, VII, IX, X as well as protein C and protein S. As protein C has the shortest half-life, warfarin therapy initially results in a prothrombotic state especially in patients who are protein C deficient and can result in thrombosis. Warfarin therapy is controlled by measuring the INR which must be maintained between 2 and 3 in patients with venous thrombosis. The INR needs to be measured twice weekly until the patient is stable, then on a regular basis with warfarin dose adjustment ideally in a warfarin dosing clinic. Diet and medication can affect the INR and counselling the patient is mandatory. The duration of warfarin therapy for a venous thrombosis is individualised and partly dependent on the underlying risk factor/s. If for example there is an obvious cause e.g. knee surgery and no other risk factors, a reasonable duration would be 3–6 months. If there is a strong family history of thrombosis and the patient had a spontaneous thrombosis a reasonable period of anticoagulation would be for at least 9 months. Persistence of an elevated D-dimer level is also an indication for ongoing anticoagulation therapy but the bleeding risk is assessed in all patients on anticoagulation therapy. Prophylaxis Venous thromboembolism (VTE) prophylaxis consists of pharmacologic and non- pharmacologic measures to diminish the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) which are applied during high risk situations such as major orthopaedic surgery. Many VTE prophylaxis and therapeutic guidelines are available e.g. Jacobson BF, Louw S, Buller H, et al. Venous thromboembolism: prophylactic and therapeutic practice guideline. S Afr Med J. 2013;103(4 Pt 2):261-7.