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| ==[[Heparin-induced thrombocytopenia history and symptoms | History and symptoms]]== | | ==[[Heparin-induced thrombocytopenia history and symptoms | History and symptoms]]== |
| ==[[Heparin-induced thrombocytopenia lab tests | Lab tests]]== | | ==[[Heparin-induced thrombocytopenia lab tests | Lab tests]]== |
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| ==Treatment== | | ==Treatment== |
| ==[[Heparin-induced thrombocytopenia medical therapy | Medical therapy]]== | | ==[[Heparin-induced thrombocytopenia medical therapy | Medical therapy]]== |
| Treatment is by prompt withdrawal of heparin and replacement with a suitable alternative anticoagulant. To block the thrombotic state, [[lepirudin]], [[fondaparinux]], [[bivalirudin]], [[argatroban]], [[danaparoid]] or other [[direct thrombin inhibitor]]s are used. [[Low molecular weight heparin]] is deemed contraindicated in HIT.
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| According to past reviews, patients treated with lepirudin for heparin-induced thrombocytopenia showed a relative risk reduction of clinical outcome (death, amputation, etc.) to be 0.52 and 0.42 when compared to patient controls. In addition, patients treated with argatroban for HIT showed a relative risk reduction of the above clinical outcomes to be 0.20 and 0.18. <ref>{{cite journal |author=Hirsh J, Heddle N, Kelton J |title=Treatment of heparin-induced thrombocytopenia: a critical review |journal=Arch Intern Med |volume=164 |issue=4 |pages=361-9 |year=2004 |pmid=14980986}}
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| .</ref>
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| == Pharmacotherapy ==
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| === Acute Pharmacotherapies ===
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| * Check platelet counts twice weekly while on heparin. Withdrawal heparin immediately of HIT is suspected. Platelet transfusion worsens thrombosis and should be reserved for patients with active bleeding. [[Warfarin]] therapy should be avoided for 3-5 days after [[heparin]] cessation and/or until [[thrombocytopenia]] resolves (>100,000).
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| * Use of direct thrombin inhibitors is the safest and most effective therapeutic approach to HIT for both those who need ongoing anticoagulation and for thrombosis prevention.
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| Danaproid (Orgaran) is a heparinoid composed of 85% heparan sulphate, 10% dermatan sulphate and 5% [[chondroitin sulphate]] that has approximately 10% cross reactivity with [[heparin]]. It has been shown to reduce mortality from thrombotic complications to 5% from 28%.
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| * The in vitro cross reactivity of LMWH with heparin dependent antibodies is approximately 60-100%. Some argue that LMWH is contraindicated for patients who develop HIT because of this cross-reactivity. Nonetheless, a theoretical argument for the use of [[LMWH]] in therapy for HIT has been made. The theory is that the [[LMWH]] overall interaction of [[heparin]] with PF4 will diminish. Though there are reports of [[LMWH]] being effective in controlling HIT in the presence of cross-reacting antibodies, the consensus is not to administer LMWH unless the absence of cross reactivity has been determined.
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| As stated before when HIT is suspected it is recommended to discontinue the heparin and initiate other agents such as direct thrombin inhibitors (DTIs; agatroban, hirudin & bivalirudin). Agatroban (AKA Novastan) doesn't resemble heparin and therefore won't cross-react with heparin antibodies. It is a medication specifically designed as a synthetic intravenous thrombin inhibitor, derived from arginine, to be an anticoagulant in patients with HIT. It is hepatically eliminated (t1/2 = 1 hour). It is contraindicated in patients with problems of hemorrhage and one should avoid intramuscular injections during its use. The infusion is initiated at 2 ug/kg/min; in patients with hepatic impairment it is recommended to reduce the dose to 0.5 ug/kg/min. Adjustment is made to a steady state aPTT of 1.5-3X the baseline. With this regimen greater than half of patients had platelet counts recover by day 3 (in HIT). Abrupt discontinuation of agatroban can lead to a hypercoagulable state. With administration its effects are immediate and a steady state can be achieved in 1-3 hours. When agatroban is given it is advised to begin coumadin. When the INR is >4 discontinue the agatroban and recheck the INR 4-6 hours later. If the INR is below the therapeutic range then resume agatroban. Avoid prothrombotic problems by overlapping the coumadin and agatroban. It has no cross-reactivity with HIT antibodies (to PF4). There is no antibody formation after repeated administration. It does not require dose adjustment in renal impairment.
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| Lepirudin is a DTI but, unlike agatroban, it is eliminated by the kidneys.
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| Hirudin binds to the active site of thrombin by exosite 1, the site at which thrombin binds to its substrates.
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| Bivalrirudin, like hirudin, binds to the active site of thrombin/exostie 1.
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| Coumadin (and vitamin K antagonists generally) are recommended for long-term anticoagulation however they should not be administered too early, unopposed or in excessive doses. It is important not to initiate coumadin treatment until the platelet count has recovered due to the threat of skin necrosis or gangrene. Discontinuing the heparin and giving Coumadin doesn't prevent the onset of thrombosis in ~50% of patients. Once thrombocytopenia has resolved the coumadin can then be given at a low maintenance dose and alternative anticoagulation should be continued along with coumadin for at least 5 days. The alternative anticoagulant should not be discontinued until the platelet count has achieved a stable plateau and the INR has been the therapeutic range for at least 2 days. The optimal duration of the anticoagulation has not been established.
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| == Patients Undergoing Surgery or PCI ==
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| Patients with HIT should be treated with [[Bivalirudin]], a direct thrombin inhibitor to support these procedures.
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| == Secondary Prevention == | | == Secondary Prevention == |
| Patients with HIT should be treated with [[Bivalirudin]], a direct thrombin inhibitor to support future procedures. | | Patients with HIT should be treated with [[Bivalirudin]], a direct thrombin inhibitor to support future procedures. |