Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 14-04: Increased Platelet Destruction + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Thrombocytopenia within 5–14 days of exposure to heparin Decline in baseline platelet count of 50% or greater Thrombosis occurs in up to 50% of cases; bleeding is uncommon +++ General Considerations ++ Affects approximately 3% of patients exposed to unfractionated heparin and 0.6% of patients exposed to low-molecular-weight heparin (LMWH) Results from formation of IgG antibodies to heparin-platelet factor 4 (PF4) complexes; the antibody:heparin-PF4 complex binds to and activates platelets independent of physiologic hemostasis, which leads to thrombocytopenia and thromboses + Clinical Findings Download Section PDF Listen +++ ++ Patients are often asymptomatic Bleeding usually does not occur due to the pro-thrombotic nature of HIT Thrombosis (at any venous or arterial site), however, may be detected in up to 50% of patients, up to 30 days post-diagnosis + Diagnosis Download Section PDF Listen +++ ++ If thrombosis has not already been detected, the use of duplex Doppler ultrasound of the lower extremities should be considered to rule out subclinical deep vein thrombosis (DVT) A presumptive diagnosis of HIT is made when new-onset thrombocytopenia is detected in a patient (typically a hospitalized patient) within 5–14 days of exposure to heparin Other presentations (eg, rapid-onset HIT) are less common A decline of ≥ 50% or more from the baseline platelet count is typical The 4T score is a clinical prediction rule Can be found at http://www.qxmd.com/calculate-online/hematology/hit-heparin-induced-thrombocytopenia-probability Assesses pretest probability for HIT However, low scores have been shown to be more predictive of excluding HIT, than are intermediate or high scores of predicting its presence When HIT is clinically suspected, a screening PF4-heparin antibody enzyme-linked immunosorbent assay (ELISA) must be performed to establish HIT diagnosis If this PF4-heparin antibody ELISA is positive, the diagnosis must be confirmed using a functional assay (such as serotonin release assay) The magnitude of a positive ELISA result correlates with the clinical probability of HIT + Treatment Download Section PDF Listen +++ ++ Initiate as soon as the diagnosis of HIT is suspected, before results of laboratory testing is available Management of HIT (Table 14–5) involves the immediate discontinuation of all forms of heparin Despite thrombocytopenia, platelet transfusions are rarely necessary and should be avoided Fondaparinux is a reasonable option for clinically stable patients Direct thrombin inhibitor (DTI) Preferred in critical illness because of the shorter duration of action Argatroban should be administered immediately due to substantial frequency of thrombosis among HIT patients Should be continued until the platelet count has recovered to at least 100,000/mcL, at which point treatment with a vitamin K antagonist (warfarin) may be initiated Continue the DTI until therapeutic anticoagulation with warfarin has been achieved (international normalized ratio [INR] of 2.0–3.0) Infusion of argatroban must be temporarily discontinued for 2 hours before the INR is obtained so that it reflects the anticoagulant effect of warfarin alone Warfarin In all patients with HIT, some form of anticoagulation (warfarin or other) should be continued for at least 30 days because of a persistent risk of thrombosis even after the platelet count has recovered In patients in whom thrombosis has been documented, anticoagulation should continue for at 3–6 months ++Table Graphic Jump LocationTable 14–5.Management of suspected or proven HIT.View Table||Download (.pdf) Table 14–5. Management of suspected or proven HIT. I. Discontinue all forms of heparin. Send PF4-heparin ELISA (if indicated). II. Begin treatment with direct thrombin inhibitor, or in some circumstances, fondaparinux. Agent Indication Dosing Argatroban Prophylaxis or treatment of HIT Continuous intravenous infusion of 0.5–1.2 mcg/kg/min, titrate to aPTT = 1.5 to 3 × the baseline value.1 Max infusion rate ≤ 10 mcg/kg/min. Bivalirudin Percutaneous coronary intervention2 Bolus of 0.75 mg/kg intravenously followed by initial continuous intravenous infusion of 1.75 mg/kg/h. Manufacturer indicates monitoring should be by ACT. Fondaparinux Treatment of HIT 5–10 mg (weight based) III. Perform Doppler ultrasound of lower extremities to rule out subclinical thrombosis (if indicated). IV. Follow platelet counts daily until recovery occurs. V. When platelet count has recovered, transition anticoagulation to warfarin or fondaparinux; treat for 30 days (HIT) or 3–6 months (HITT). VI. Document heparin allergy in medical record (confirmed cases). 1Hepatic insufficiency: initial infusion rate = 0.5 mcg/kg/min.2Not approved for HIT/HITT.ACT, activated clotting time; aPTT, activated partial thromboplastin time; ELISA, enzyme-linked immunosorbent assay; HIT, heparin-induced thrombocytopenia; HITT, heparin-induced thrombocytopenia and thrombosis; PF4, platelet factor 4. + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ Subsequent exposure to heparin should be avoided in all patients with a prior history of HIT, if possible If its use is regarded as necessary for a procedure, it should be withheld until PF4-heparin antibodies are no longer detectable by ELISA (usually as of 100 days following an episode of HIT), and exposure should be limited to the shortest time period possible +++ When to Refer ++ All patients should be evaluated by a hematologist +++ When to Admit ++ Most patients with HIT are hospitalized at the time of detection of thrombocytopenia An outpatient in whom HIT is suspected should typically be admitted because the DTIs must be administered by continuous intravenous infusion However, in selected cases, if they are a candidate for fondaparinux, admission is a clinical decision + References Download Section PDF Listen +++ + +Cuker A et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360–92. [PubMed: 30482768] + +Cuker A et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012 Nov 15;120(20):4160–7. [PubMed: 22990018] + +Schindewolf M et al. Use of fondaparinux off-label or approved anticoagulants for management of heparin-induced thrombocytopenia. J Am Coll Cardiol. 2017 Nov 28;70(21):2636–48. [PubMed: 29169470] + +Warkentin TE. Laboratory diagnosis of heparin-induced thrombocytopenia. Int J Lab Hematol. 2019 May;41(Suppl 1):15–25. [PubMed: 31069988]