Introduction:
Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition mediated by platelet-activating antibodies that target platelet factor 4 (PF4) and heparin complexes. Heparin is a universal medication in cardiopulmonary bypass (CPB) patients exposed to heparin and experiencing a postoperative platelet count fall. Thrombocytopenia is considered a fall in the platelet count of less than 150,000 per cubic millimeter.
What Does the Heparin Drug Do to the Blood?
Heparin is the parenteral anticoagulant drug, a sulfated and non-uniform mixture of straight-chain mucopolysaccharide. It has a major anticoagulant effect by inactivating thrombin and blocking mostly Xa and XIIa through an antithrombin (AT) dependent mechanism. Heparin binds to AT III (antithrombin III) through a high-affinity pentasaccharide. It forms a heparin- AT III complex, which binds to the clotting factors of intrinsic and common pathways and inactivates them but not the extrinsic pathway, which is present on about a third of heparin molecules. By inactivating thrombin, heparin prevents fibrin formation and inhibits thrombin-induced activation of platelets and factors V and VIII.
What Is Heparin-Induced Thrombocytopenia (HIT)?
Heparin-induced thrombocytopenia (HIT) is a fetal complication of heparin exposure caused by platelet-activating IgG antibodies that identify multimolecular complexes of platelet factor 4 (PF4) and heparin. It is seen five to ten days after starting heparin therapy. It causes the platelet count to be less than 1,00,000 / ul or decrease by less than 50 %. It mostly occurs due to the formation of antibodies against the complex of heparin with the platelet factor and results in paradoxical thrombosis, which is usually seen with unfractionated heparin long-term usage.
Type I, also known as heparin-associated thrombocytopenia, is a mild form not associated with an increased risk of thrombosis with an unknown mechanism of HIT and is non-immune, likely related to its platelet pro-aggregating effect, which is marked by mild and transient asymptomatic thrombocytopenia seldom less than 100,000 platelets/μL mainly develops early within the first two days of beginning with heparin therapy and disappears equally rapidly once the heparin is withdrawn. Whereas HIT type II is immune-mediated and associated with a risk of thrombosis.
How to Manage Patients With Heparin-Induced Thrombocytopenia?
HIT is a devastating immunological adverse drug response provoked by the emergence of antibodies that activate platelets in the presence of heparin. A bi-phasic platelet count pattern is characteristic of heparin-induced thrombocytopenia (HIT). Heparin-PF4 (platelet factor 4) antibody testing is used in patients with clinical suspicion of heparin-induced thrombocytopenia. However, the laboratory diagnosis is also challenging because of the high commonness of anti-PF4/heparin antibody seropositivity after cardiac bypass surgery in patients without heparin-induced thrombocytopenia. Therefore, functional tests and immunoassays are employed to demonstrate heparin-induced thrombocytopenia (HIT) antibodies. Functional tests estimate platelet activity in the presence of the patient's serum, which comprises:
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Heparin‐Induced Platelet Aggregation (HIPA): It has a sensitivity of 35 to 85 %, is easier to perform, and, thus, is commonly used.
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Serotonin Release Assay (SRA): It has a sensitivity rate of 95 % and is specific but is more complex and technically demanding.
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Flows Cytometric Assays: Detects platelet microparticle release.
The immunoassays use the ELISA (immuno‐enzymatic tests) to detect the HIT antibody that binds to the PF4–heparin complex, which has a high sensitivity rate of 80 % to 100 % but low specificity. Treatment involves discontinuation of heparin and initiation of a non-heparin anticoagulant. Doctors must depend on an assortment of clinical assessments and laboratory testing to differentiate patients with true heparin-induced thrombocytopenia (HIT) from multiple patients with thrombocytopenia due to other causes.
What Is the Management of Heparin-Induced Thrombocytopenia (HIT) During Cardiac or Vascular Surgery?
The American College of Chest Physicians, in collaboration with the College of American Pathologists, has passed a guideline for the monitoring of the platelet count is recommended for most patients receiving heparin treatment or who are at high risk for HIT and emphasis the platelet count should be inspected at least every other day from day four to fourteen of treatment or until heparin is stopped.
Treatment of HIT aims to replace heparin with an appropriate non-heparin anticoagulant.
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Warfarin: Warfarin should only be prescribed once the platelet count has recovered or there is a substantial resolution of thrombocytopenia. As warfarin predisposes to microvascular thrombosis in patients with acute heparin-induced thrombocytopenia like
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Warfarin-induced venous limb gangrene (death of body part due to lack of blood flow).
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Skin necrosis syndromes.
Reversal of warfarin anticoagulation with vitamin K is recommended when heparin-induced thrombocytopenia (HIT) is interpreted only after the start of warfarin. Avoid prophylactic platelet transfusion because it may exacerbate the hypercoagulable state, leading to additional thrombosis; however, if the patient develops bleeding or is undergoing major surgical intervention, therapeutic platelet transfusion can be considered.
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Lepirudin: Lepirudin is a recombinant anticoagulant that initiates irreversible 1:1 complexes with thrombin. Its half-life is 80 minutes and increases dramatically in renal insufficiency. It has no antidote, so it should be used cautiously or avoided completely in patients with renal compromise. The approved dose is 0.4 mg per kg (IV bolus).
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Argatroban: Argatroban is authorized to treat both heparin-induced thrombocytopenia (HIT) complicated by thrombosis and isolated HIT. It is not immunogenic like Lepirudin. The usual dose is 2 g/kg per minute, modified by APTT (activated partial thromboplastin clotting time). The drug dosage should be reduced by 75 % in patients with significant liver dysfunction as Argatroban undergoes hepatobiliary excretion. Prolongation of the INR by Argatroban is much greater than that followed by Lepirudin, which complicates Argatroban-warfarin overlap.
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Danaparoid: The drug is approved by the US Food and Drug Administration (FDA) for venous thrombosis prophylaxis after orthopedic surgery but not for treating HIT, which is the combination of heparin and glycosaminoglycans such as dermatan and chondroitin sulfates. It exerts anticoagulant effects primarily by inhibiting factor Xa and inhibiting thrombin to a much lesser degree. The drug has a long half‐life with 100 % bioavailability and is cleared renally. The suggested dose for thromboprophylaxis in heparin-induced thrombocytopenia (HIT) patients without thrombosis is 750 U, administered subcutaneously.
Conclusion:
Heparin is an anticoagulant drug broadly used for thromboprophylaxis or for treating many thromboembolic conditions and surgery like cardiovascular surgery and invasive procedures. Nevertheless, heparin is related to causing severe adverse effects, including heparin-induced thrombocytopenia (HIT), a common, serious, and potentially life-threatening condition depicted as a decrease in platelet count during or shortly following exposure to heparin.
