Introduction:
Heparin is a blood thinner (anticoagulant) that prevents the formation of blood clots. Heparin prevents blood clots caused by a disease or a condition. It is used as a prophylactic agent before surgeries to reduce blood clots during the procedure and prevent post-surgical complications. It prevents coagulation during cardiac surgery, dialysis, and continuous renal replacement therapy. It is a prescription drug. It is available in an intravenous form in the hospital. It works by disrupting the formation of blood clots in the veins. It prevents blood clots from forming or stopping clots from getting more significant. Heparins avoid deep vein thrombosis and pulmonary embolism in high-risk patients undergoing surgery, stroke, and other immobilized patients.
What Is Thrombocytopenia?
It is a condition that occurs when the bone marrow does not make enough platelets (they are large cells in the bone marrow that helps make blood clots). As a result, the bleeding is continuous in these patients. Platelets stop bleeding by forming blood clots in the blood vessel. Thrombocytopenia can occur due to bone marrow disorders such as leukemia (cancer of the white blood cells produced from the bone marrow). It can be mild and cause few signs and symptoms. However, internal bleeding can sometimes be deficient, and dangerous internal bleeding can occur.
What Is Heparin-Induced Thrombocytopenia?
It is an immune-mediated adverse drug reaction caused by the antibodies that activate the platelets in the presence of heparin. It results in the dropping of platelet levels. In addition, the high clotting due to the antibodies causes large blood clots. In some cases, the heparin triggers a reaction that causes the blood to clot excessively instead of preventing clots. The reaction causes the platelet levels to drop. It is also called heparin-induced thrombocytopenia and thrombosis (HIIT). Approximately five percent of people develop this condition and are under heparin therapy for more than five days. Heparin can develop heparin-induced thrombocytopenia irrespective of frequency or dose.
What Are the Types of Heparin-Induced Thrombocytopenia?
There are two types of heparin-induced thrombocytopenia. They are:
-
HIT I- Which is a less severe form. It does not cause severe complications.
-
HIT II- Heparin binds to the molecule called the platelet factor 4 (PF4). In type II, the antibodies attack this pairing, resulting in more activation of platelets. The reaction causes platelet levels to drop and puts them at risk of developing severe blood clots.
What Are the Signs and Symptoms of Heparin-Induced Thrombocytopenia?
About half of the people with HIT develop a new blood clot, such as a deep vein thrombosis (DVT) or pulmonary embolism(PE).
Symptoms include:
-
Sudden sharp pain in the chest.
-
High blood pressure.
-
Feeling faint, dizzy, or light-headed.
-
Rapid heartbeat.
-
Coughing and wheezing.
-
Feeling out of breath.
-
Excessive sweating.
-
Fever and chills.
-
Pain, swelling, redness, or tenderness in the arm or leg.
-
Soreness or a rash and pain at the injection site where the patient received heparin.
What Is the Mechanism of Heparin-Induced Thrombocytopenia (HIT)?
-
Anyone taking any type of heparin at any dose is at risk of developing HIT antibodies but will not necessarily develop the clinical syndrome of HIT.
-
The platelets form blood clots by thrombin formation. Therefore, HIT is caused by the appearance of antibodies that activate platelets against the antigen following heparin administration.
-
The antigen (the molecule against which the antibodies react) is a combination of heparin and platelet factor 4 (PF4) found in the granules of the platelets.
-
When heparin binds with the platelet factor 4, it changes and becomes immunogenic, producing heparin P4 antibodies that are HIT antibodies.
-
The heparin P4 IgG complex activates the platelets and releases prothrombotic platelet particles. These microparticles cause excessive thrombin generation, resulting in thrombosis (formation of blood clots).
-
These processes contribute to the activation of the coagulation cascade and thrombin generation. HIT is due to the antibody-coated platelets by the reticuloendothelial system (blood system).
-
Eight percent of people with heparin are at risk of building HIT antibodies. The fall in the platelets starts 5-14 days after the initiation of heparin.
-
The onset can be rapid or delayed. If the patient has circulating heparin (PF4) antibodies from a recent heparin exposure, the platelet count may drop within hours or minutes, resulting in rapid onset HIT.
-
The platelets rise within two to three days and return to normal within four to ten days after the cessation of heparin treatment. It takes another two to three hours for antibodies to disappear. Therefore, worsening thrombocytopenia must be investigated despite the discontinuation of heparin.
-
HIT can cause thromboembolic complications such as deep vein thrombosis, pulmonary embolism, thrombotic stroke, myocardial infarction, and occlusion of limb artery requiring amputation.
-
Pulmonary embolism and deep vein thrombosis occur in postoperative patients. Arterial thrombosis occurs more frequently than venous thrombosis for cardiovascular diseases.
-
Other complications include necrotizing skin lesions at the injection site in 10 to 20 percent of patients, characterized by chills, hypertension, fever, chest pain, tachycardia, and dyspnoea with circulatory HIT antibodies. In addition, females are more likely to suffer from thrombotic stroke.
What Are the Diagnostic Tests for Heparin-Induced Thrombocytopenia?
The following diagnostic tests are done to detect HIT-
- Platelet Levels - Normal platelet count is taken. The platelet levels reveal whether the patient has low platelets or thrombocytopenia.
- Clot Formation - Blood tests can detect if there is clot formation.
- PF4 Antibody Levels - The PF4 antibody levels in the blood can confirm whether the immune system is activating the platelets. HIT antibodies are demonstrated in vitro by functional tests and immunoassays. They include heparin-induced platelet aggregation (HIPA), the serotonin release assay (SRA), and flow cytometric assays that detect platelet microparticle release. The immunoassays use ELISA (enzyme-linked immunosorbent assay) to see the HIT antibody that binds to the PF4- heparin complex. Ultrasounds screen the legs for blood clots (deep vein thrombosis). The imaging is performed on arms as well.
What Is the 4TS Test in Heparin-Induced Thrombocytopenia?
The 4Ts test gives information about the condition. Higher the score, the greater the risk for HIT. The physician assigns a score (from 0 points to 2 points) for the following criteria:
-
Thrombocytopenia
-
Timing of reaction to heparin
-
Thrombosis
-
Other causes of thrombocytopenia
What Is the Treatment for Heparin-Induced Thrombocytopenia?
Treatment includes switching to a different blood thinner. The platelet count should start increasing within a few days of heparin. Alternatives to heparin are prescribed to prevent blood clots. Once the platelet count has returned to normal, warfarin is prescribed. Immediate cessation of heparin is mandatory, including heparin-coated catheters, heparinized dialysate, and heparin flushes. The thrombotic event and platelet count are monitored. Warfarin should be given once the platelet count has recovered. Warfarin is not recommended early in HIT because it can worsen thrombosis and cause skin necrosis and venous limb gangrene. Platelet transfusion is avoided because it can exacerbate the coagulation cascade. However, therapeutic platelet transfusion is considered if the patient is undergoing restorative surgery. The alternative drugs for HIT include Danaparoid, Lepirudin, Argatroban, direct thrombin inhibitors (Argatroban, Bivalirudin), and Fondaparinux.
Conclusion:
Bleeding is one of the significant concerns with direct thrombin inhibitors. Surgical thromboembolectomy or systemic or local thrombolysis is an adjunctive treatment alternative to parenteral anticoagulation. HIT can be prevented by limiting the courses of heparin to less than five days and using low molecular weight heparin for prevention in high-risk patients. A physician should sign it in the patient's medical history by taking proper records of heparin flushes and normal heparinized saline.
