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![DANAPAROID
Danapariod sodium is a synthetic heparinoid compound prepared from a porcine intestinal
source and consist of heparin sulfate (84%) dermaltan sulfate (12%) and chondroitin sulfate
(4%).
It produce the anticoagulant effect primarily via inhibition of factor Xa.
The incidence of cross reactivity with HIT antibodies is significantly lower with Danapariod.
Elimination dependent on kidney.
No reversal agent for this drug.
Bleeding and transfusion requirement were observed.
Intermittent bolus doses and continuous infusion
Risk Factors
Inadequate anticoagulation [formation of clot]
Severe postope bleeding
Large quantities of blood transfusion
Low molecular weight with a long half life 118-24 hrs}
Monitoring via anti Xa levels and currently no antidote
It can be useful in the management of HIT after cardiac surgery](https://image.slidesharecdn.com/hitppt-240723111307-1116d918/85/Heparin-Thrombocytopenia-Presentationppt-6-320.jpg)
![ Argatroban:
Widely used in pts with HIT who requires percutaneous coronary interventions.
It is a synthetic direct thrombin inhibitor that binds reversibly to the active
site of thrombin molecule.
Primarily metabolized by liver.
Short half life 39-59 mins which is prolonged in pts with moderate
impairment [152 mins]
Disadvantages:
Bleeding / clotting
No monitoring device](https://image.slidesharecdn.com/hitppt-240723111307-1116d918/85/Heparin-Thrombocytopenia-Presentationppt-10-320.jpg)
Heparin Thrombocytopenia Presentationppt
- 1. Alternative to Heparin & HeparinThrombocytopenia By Deepanshu Pilwan MSc Cardiac Perfusion 1st year Presented to Dr Ujjwal Chowdhury
- 2. Contents Introduction Alternativeto Heparin Defibrinogenating agents Direct thrombin inhibitors HEPARIN INDUCED THROMBOCYTOPENIA History Clinical Conditions/Causes of Thrombocytopenia Types of HIT Frequency Clinical events/Complications associated with HIT Treatment of HIT
- 3. INTRODUCTION Anticoagulation isrequired for any form of extracorporeal circulation to prevent activation of the coagulation system by contact between blood and artificial biological surfaces. Cpb circuits are comprise of a large surface area of mainly plastic material which if left come to contact with blood without appropriate anticoagulation would result in formation of clots. Inadequate anticoagulation is most serious form lead to death. Lesser forms lead to impairment of organ function usually neurological and renal dysfunction. Heparin is the most commonly used anticoagulant in the context of cpb.
- 4. ALTERNATIVE TO HEPARIN Lowmolecular weight heparin: Different components of UF heparin poses differing affinities for platelets and AT-IlI. UF heparin contains polysaccharides chains with molecular weight above 5,400 and has anti factor Xa and anti thrombin action in the ratio of 1:1. LMWH are less capable of inhibiting thrombin factor Xa. Moderate inhibition factor Xa prevents thrombus formation without impairing haemostasis. Reduce protein binding may enhance the bioavailability of LMWH LMWH has longer plasma life compared to UFH 110 to 200 mins. Renal excretion is the principal route of elimination. Mean molecular weight 4,000-6,500Da. LMWH has been used in prevention of deep vein thrombosis during hemodialysis and in the treatment of thrombosis occurring HIT.
- 5. Risk Factors Postoperative bleeding Blood loss is significantly more in patients who received LMWH with in 12 hours of surgery Transfusion must be weighted against the risk of ischemia LMWH is discontinued more than 12 hours before operation LMWH are not recommended for use in HIT Patients
- 6. DANAPAROID Danapariod sodiumis a synthetic heparinoid compound prepared from a porcine intestinal source and consist of heparin sulfate (84%) dermaltan sulfate (12%) and chondroitin sulfate (4%). It produce the anticoagulant effect primarily via inhibition of factor Xa. The incidence of cross reactivity with HIT antibodies is significantly lower with Danapariod. Elimination dependent on kidney. No reversal agent for this drug. Bleeding and transfusion requirement were observed. Intermittent bolus doses and continuous infusion Risk Factors Inadequate anticoagulation [formation of clot] Severe postope bleeding Large quantities of blood transfusion Low molecular weight with a long half life 118-24 hrs} Monitoring via anti Xa levels and currently no antidote It can be useful in the management of HIT after cardiac surgery
- 7. DEFIBRINOGENATING AGENTS Ancrod Ancrod is derived from malayan pit viper venom. It lyses fibrinogen there by preventing formation of fibrin polymers. The avg dose used was 1.65 U/Kg. Elimination by reticulo endothelial system may take several days. It has also been used in pts with acute HIT undergoing cardiac surgical procedures. Disadvantages No antidote Lack of monitoring Bleeding and increase need for homologous blood products Postope thrombotic complications Fibrinogen concentrate and Fresh frozen plasma need to administered to restore fibrinogen levels
- 8. DIRECT THROMBIN INHIBITORS Hirudin: Isolated from the salivary glands of leech and it inhibits thrombin directly without requiring AT Ill. Lepirudin has been used more commonly. It is effective in inhibiting free as well as clot bound thrombin. Elimination primarily by the kidneys and plasma half life may be prolonged as long as 120 hours (nrml -80 mins)in the presence of renal failure. MUF may be utilised to enhance the elimination of hirudin during cpb. Disadvantages: No effective reversal agent Excessive bleeding can occur with renal insufficiency Anaphylactic reactions Eliminated by hemofilter
- 9. Bivalirudin: Itis a bivalent direct thrombin inhibitor that inhibits free as well as clot bound thrombin thus preventing thrombin mediated platelet activation. Half life app 25 to 30 mins. No antidote It primarily undergoes dual elimination via proteolytic cleavage andrenal elimination. Elimination improved by hemofiltration. Dosing protocol 1 to 1.5 mg/kg ,50 mg added to the pump. Clotting may be observed in the pericardium. Disadvantages: Bleeding complications Risk of clot formation in the cpb circuit
- 10. Argatroban: Widelyused in pts with HIT who requires percutaneous coronary interventions. It is a synthetic direct thrombin inhibitor that binds reversibly to the active site of thrombin molecule. Primarily metabolized by liver. Short half life 39-59 mins which is prolonged in pts with moderate impairment [152 mins] Disadvantages: Bleeding / clotting No monitoring device
- 11. Heparin ≤platelet inhibitors : Administration of a potent platelet inhibitor immediately before heparinization with UFH is another method used to manage HIT patients undergoing cardiac surgery. Platelet count was maintained pre operative and no significant thrombotic or bleeding complications Infusion of epoprostenol (15-30 mg/kg/min)
- 12. HEPARIN INDUCED THROMBOCYTOPENIA Heparin induced thrombocytopenia (HIT) is characterized by a decrease in the platelet count of more than 50% from the highest platelet count value after the start of heparin, an onset 5 to 10 days after the start of heparin, hypercoagulability, and the presence of heparin dependent, platelet activating gG antibodies. HIT is an immune-mediated potentially fatal syndrome in which the heparin- induced immunoglobulins bridge platelets causing both thrombocytopenia and thrombosis. HIT does not induce bleeding but rather results in a paradoxical prothrombotic state. HIT is more common in surgical than medical patients (especially cardiac and orthopaedic patients).
- 13. In casesof suspected HIT, it is crucial to promptly discontinue all forms of heparin to prevent further platelet activation. Alternative anticoagulation strategies should be initiated, such as transitioning to a non-heparin anticoagulant like argatroban, bivalirudin, fondaparinux, or direct oral anticoagulants (DOACs) depending on the patient's clinical condition and kidney function. Prompt recognition and management of HIT are essential to prevent thrombotic complications like deep vein thrombosis, pulmonary embolism, or even arterial thrombosis. Close collaboration between healthcare providers, hematologists, and clinical pharmacists is vital in managing patients with HIT to ensure appropriate treatment and prevent associated risks.
- 14. History Heparin causingthrombocytopenia was reported by several investigators in 1940s. Thrombotic complications with heparin therapy was observed by Weisamn and Tobin in 1958 but did not mention thrombocytopenia. Link between thrombocytopenia and thrombosis was first noted by Rhodes and his colleagues in 1973
- 15. Clinical Conditions/Causes ofThrombocytopenia 1. Increased platelet destruction: Non-immune Septicemia/ Inflammation Disseminated intravascular coagulation Thrombotic thrombocytopenic purpura Immune Autoimmune: idiopathic or secondary immune thrombocytopenia Alloimmune: post-transfusion purpura Drug-induced: prothrombic (heparin), prohemorrhagic (quinine, quinidine, gold, sulfa antibiotics, rifampin, vancomycin, NSAIDs, many others) 2. Decreased platelet production: Alcohol, cytotoxic drugs Aplastic anemia
- 16. Leukemia, myelodysplasia Metastatic invasion of marrow Certain infections 3. Hypersplenism 4. Hemodilution (infusion of blood products, colloids, or crystalloids)
- 17. Types of HIT Twotypes of HIT emerged in the 1980s First group had early onset and mild thrombocytopenia, asymptomatic with no heparin dependent IgG antibodies this was referred to as Type 1 HIT now referred to as non immune heparin associated thrombocytopenia. Second group had delayed onset severe thrombocytopenia with presence of heparin dependent IgG antibody this was referred to as Type 2 HIT i.e. immune- mediated HIT.
- 18. Frequency 1. HIT Type1 Difficult to assess as patient might have already activated platelets from cormorbid conditions; surgery, infection etc. Some early studies suggest it might be as high as 30%HIT 2. Type 2 0.2-10% Female > male Dose duration: Ab develop from D4 to peak at D7, most patient develop HIT while receiving heparin. Risk increases with ≥5 of heparin therapy. Heplock and heparin coated device have been implicated in development of antiPF4/Heparin Ab.
- 21. Clinical events/Complications associated withHIT Deep venous thrombosis Pulmonary embolism Myocardial infarction Occlusion of limb arteries (possibly resulting in amputation) Transient ischemic attack and stroke Skin necrosis End-organ damage (eg, adrenal, bowel, spleen, gallbladder, or hepatic infarction; renal failure) Death
- 22. Treatment of HIT The treatment of heparin-induced thrombocytopenia (HIT) involves primarily the immediate cessation of all forms of heparin. Once HIT is suspected, heparin should be discontinued promptly to prevent further platelet activation and thrombotic complications. After stopping heparin therapy, alternative anticoagulants should be initiated to manage thrombosis and prevent clotting. Options for anticoagulation in the setting of HIT include: 1. Direct Thrombin Inhibitors: Agents like argatroban, bivalirudin, and lepirudin are commonly used as they do not rely on antithrombin for their anticoagulant effects. These are often the preferred choice in HIT. 2. Factor Xa Inhibitors: Alternatives such as fondaparinux, danaparoid, and direct oral anticoagulants (DOACs) like rivaroxaban or apixaban may also be considered in specific cases. 3. Platelet Activation Inhibitors: Agents like dipyridamole or aspirin may be used in some instances.
- 23. Management of HITalso involves close monitoring of platelet counts and clinical assessment for signs of thrombosis. Individualized care and assessment by a hematologist or a specialist in hemostasis are essential in the management of HIT to determine the appropriate anticoagulant therapy and monitoring plan. It is crucial to educate patients about the potential complications of HIT, ensure proper medication management, and monitor for any signs of thrombosis or bleeding. Collaboration between healthcare providers, including hematologists, pharmacists, and other specialists, is vital in the comprehensive treatment and management of HIT.
- 24.