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CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
CME: Bleeding Disorders - Management
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CME: Bleeding Disorders - Management

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  • 1. Prof.Dr.G.Sundaramurthy’s unit Dr.K.Senthamizh selvan
  • 2.  
  • 3. <ul><li>ARTEFACTUAL THROMBOCYTOPENIA </li></ul><ul><li>INCREASED PLATELET DESTRUCTION </li></ul><ul><li>DECREASED PLATELET SYNTHESIS </li></ul><ul><li>ABNORMALITY IN PLATELET FUNCTION </li></ul>
  • 4. <ul><li>autoimmune- primary/idiopathic </li></ul><ul><li>-secondary causes(SLE,drugs) </li></ul><ul><li>alloimmune </li></ul><ul><li>non-immunologic(TTP,DIC,HUS) </li></ul><ul><li>Abnormal vascular surfaces </li></ul>
  • 5. <ul><li>---- treatment options </li></ul><ul><li>STEROIDS : </li></ul><ul><li>-reduces Ab production </li></ul><ul><li>-increases marrow platelet production </li></ul><ul><li>-reduces intramedullary platelet destruction </li></ul><ul><li>-reduces splenic sequestration </li></ul><ul><li>-down regulates macrophage Fc R </li></ul>
  • 6. &nbsp;
  • 7. &nbsp;
  • 8. <ul><li>SPLENECTOMY : </li></ul><ul><li>removes primary destruction site of platelets </li></ul><ul><li>reduces antibody production </li></ul><ul><li>IV Ig: </li></ul><ul><li>- blocks Fc R in macrophages ,B cells </li></ul><ul><li>- improves cell survival by modulating growth factors </li></ul><ul><li>ANTI –D immunoglobulin : </li></ul><ul><li>- coats RBCs of Rh +ve patients ,causes Fc R mediated destruction in spleen </li></ul><ul><li>- hence spares platelets </li></ul><ul><li>- efficacy is low after splenectomy </li></ul>
  • 9. <ul><li>DANAZOL: </li></ul><ul><li>- down regulates Fc R on phagocytic cells </li></ul><ul><li>RITUXIMAB: </li></ul><ul><li>- anti CD 20 antibody –causing selective B cell depletion in vivo </li></ul><ul><li>-mechanism- apoptosis </li></ul><ul><li>ADCC </li></ul><ul><li>complement mediated </li></ul><ul><li>VINCA ALKALOIDS: </li></ul><ul><li>- inhibition of microtuble dependant events required for monocytes/macrophages </li></ul>
  • 10. &nbsp;
  • 11. children adults Asymptomatic --------------------------- Prednisone 1-2mg/kg/d Minor purpura IVIg 1g/kg single dose ; High dose oral steroids ; Prednisone 1-2mg/kg/d ; Mucosal bleeding Hospital care ; IVIg 2g/kg over 2-5 days; High dose oral steroids ; Hospital care ; Prednisone 1-2mg/kg/d ; Life threatening bleed Hospital care ; IVIg 2g/kg over 2-5 days; High dose oral steroids ; Hospital care ; IVIg 1-2g/kg over 2-5 days ; Prednisone 1-2mg/kg/d ;
  • 12. <ul><li>if refractory to steroid course and splenectomy </li></ul><ul><li>options : long term IV Ig </li></ul><ul><li>pulse methylprednisolone </li></ul><ul><li>anti D immunoglobulin </li></ul><ul><li>danazol </li></ul><ul><li>vinca alkaloids </li></ul><ul><li>IFN α </li></ul><ul><li>rituximab </li></ul>
  • 13. <ul><li>ROMIPLASTIM: </li></ul><ul><li>- an Fc peptide fusion protein </li></ul><ul><li>-acts on TPO- R </li></ul><ul><li>- pathways similar to endogenous TPO </li></ul><ul><li>- given as S.C.inj </li></ul><ul><li>- used in chronic ITP </li></ul><ul><li>ELTROMBOPAG : </li></ul><ul><li>- TPO- R agonist </li></ul><ul><li>- oral route </li></ul><ul><li>- used in chronic and refractory ITP </li></ul><ul><li>-acquired amegakaryocytic TP </li></ul>
  • 14. <ul><li>gestational thrombocytopenia is a close mimicker </li></ul><ul><li>ITP is difficult to manage in pregnancy </li></ul><ul><li>anti platelet Ab – cross placenta ,causing TP in fetus </li></ul><ul><li>treatment options : IVIg </li></ul><ul><li>low dose steroids </li></ul><ul><li>splenectomy </li></ul><ul><li>mode of termination is determined by obstetric indications. </li></ul>
  • 15. <ul><li>LEVEL :1 evidence </li></ul><ul><li>quinidine,quinine,rifampicin,sulfonamides,danazol,methyldopa,acetaminophen,digoxin </li></ul><ul><li>LEVEL:2 evidence </li></ul><ul><li>goldsalts,procainamide,carbamazepine, </li></ul><ul><li>thiazides ,ranitidine,chlorpropamide </li></ul>
  • 16. <ul><li>antibody mediated </li></ul><ul><li>-complement </li></ul><ul><li>-non complement </li></ul><ul><li>idiosyncrasy </li></ul>
  • 17. <ul><li>TREATMENT OPTIONS: </li></ul><ul><li>withdrawal of offending drug </li></ul><ul><li>IV Ig </li></ul><ul><li>plasmapheresis </li></ul><ul><li>steroids </li></ul><ul><li>--- recovery within 1 wk </li></ul><ul><li>exception :gold salts induced tp which </li></ul><ul><li>takes several months for recovery </li></ul><ul><li>---dimercaprol can be tried </li></ul>
  • 18. <ul><li>3-5% of pts receiving </li></ul><ul><li>UF heparin </li></ul><ul><li>antibody to heparin- </li></ul><ul><li>platelet factor4 </li></ul><ul><li>attaches to Fc R </li></ul><ul><li>causing platelet </li></ul><ul><li>activation </li></ul><ul><li>-hypercoagulable </li></ul><ul><li>state </li></ul><ul><li>-thrombocytopenia </li></ul>
  • 19. <ul><li>TYPE :1 </li></ul><ul><li>-occurs within 2 days </li></ul><ul><li>-non immune mechanism </li></ul><ul><li>-direct effect of heparin on platelets </li></ul><ul><li>- count normalises even if treatment </li></ul><ul><li>continued </li></ul><ul><li>TYPE :2 </li></ul><ul><li>-occurs within 4-10 days </li></ul><ul><li>-immune mechanism </li></ul><ul><li>-life threatening thrombotic events </li></ul><ul><li>-we actually mean this as HIT in clinical </li></ul><ul><li>practice. </li></ul>
  • 20. <ul><li>MANAGEMENT OF HIT: </li></ul><ul><li>stop UF and LMW heparin </li></ul><ul><li>start </li></ul><ul><li>- direct thrombin inhibitors : </li></ul><ul><li>ARGATROBAN, </li></ul><ul><li>LEPIRUDIN </li></ul><ul><li>- factor 10a inhibitors - DANAPAROID </li></ul><ul><li>only these drugs are FDA approved for HIT </li></ul><ul><li>they are given for 2 weeks </li></ul>
  • 21. <ul><li>platelet count may normalise but thrombotic tendency may persist . </li></ul><ul><li>hence continued with warfarin for 3-6 months </li></ul><ul><li>warfarin induced protein C and S deficiency </li></ul><ul><li>aggravates thrombotic potential </li></ul><ul><li>-----start warfarin later </li></ul><ul><li>avoid heparin products in future for atleast 6 months. </li></ul>
  • 22. <ul><li>SLE: </li></ul><ul><li>-TP in SLE correlates with disease activity </li></ul><ul><li>-auto antibodies in SLE can bind </li></ul><ul><li>GP1b9/2b/3a </li></ul><ul><li>- treatment guidelines same as that of ITP </li></ul><ul><li>Thymoma,myasthenia,CLL,hodgkin’s disease </li></ul><ul><li>INFECTIONS : HIV,IMN,CMV,Hep B and C </li></ul><ul><li>H.pylori,varicella </li></ul><ul><li>------ to treat the primary cause </li></ul>
  • 23. <ul><li>platelets can express some epitopes due to polymorphism of gene for PL GPs </li></ul><ul><li>no natural antibodies occurs </li></ul><ul><li>1)neonatal alloimmune thrombocytopenia. </li></ul><ul><li>2)post transfusion purpura. </li></ul><ul><li>Treatment options: </li></ul><ul><li>- self limiting </li></ul><ul><li>- steroids </li></ul><ul><li>- plasmapheresis </li></ul><ul><li>- IV Ig </li></ul>
  • 24. <ul><li>ADAMTS13 --- cleaves VWF when it is conformationally unfolded </li></ul><ul><li>defect in ADAMTS13 ---causes TTP </li></ul><ul><li>1)TP </li></ul><ul><li>2)Microangiopathic hemolysis </li></ul><ul><li>3)Renal failure </li></ul><ul><li>acquired TTP </li></ul><ul><li>hereditary TTP </li></ul>
  • 25. <ul><li>ACQUIRED TTP </li></ul><ul><li>HEREDITARY TTP </li></ul><ul><li>hemodialysis </li></ul><ul><li>plasma exchange with FFP </li></ul><ul><li>plasmapheresis </li></ul><ul><li>corticosteroids </li></ul><ul><li>IV Ig </li></ul><ul><li>Immunosuppresants </li></ul><ul><li>Rituximab </li></ul><ul><li>FFP </li></ul><ul><li>plasma exchange </li></ul><ul><li>plasmapheresis </li></ul>
  • 26. <ul><li>INFECTION: </li></ul><ul><li>- Shigella dysentriae type 1 </li></ul><ul><li>- E.coli O157:H7 </li></ul><ul><li>ATYPICAL HUS: </li></ul><ul><li>no prodrome ,no apparent cause </li></ul><ul><li>MANAGEMENT </li></ul><ul><li>-BP control </li></ul><ul><li>-fluid and electrolyte balance </li></ul><ul><li>-packed cell/platelet/FFP –transfusion </li></ul><ul><li>- hemodialysis </li></ul>
  • 27. &nbsp;
  • 28. <ul><li>presents with mild bleeds </li></ul><ul><li>detected incidentally </li></ul><ul><li>not responsive to steroids/ IV Ig </li></ul><ul><li>supportive measures usually suffices in most of the cases </li></ul><ul><li>wiskott-aldrich syndrome ---requires stem cell transplantation </li></ul>
  • 29. <ul><li>1) ACQUIRED AMEGAKARYOCYTIC TP: </li></ul><ul><li>as a component of aplastic anaemia </li></ul><ul><li>CMV,Parvovirus- B19 </li></ul><ul><li>Toxins-benzene </li></ul><ul><li>TPO antibodies </li></ul><ul><li>----options </li></ul><ul><li>Platelet transfusion vincristine </li></ul><ul><li>IV Ig danazol </li></ul><ul><li>Steroids ATG </li></ul><ul><li>Cyclophosphamide allogenic BMT </li></ul>
  • 30. <ul><li>2) MARROW SUPRESSANTS : </li></ul><ul><li>Immunosupressants </li></ul><ul><li>cancer chemotherapy </li></ul><ul><li>selective megakaryocyte suppressants: </li></ul><ul><li>thiazides ,estrogens,alcohol </li></ul><ul><li>-----withdrawal of offending agent usually corrects platelet counts </li></ul><ul><li>3 ) INEFFECTIVE THROMBOPOIESIS: </li></ul><ul><li>in B12,Folate deficiency </li></ul><ul><li>-----treat the cause </li></ul>
  • 31. &nbsp;
  • 32. <ul><li>ABNORMAL PLATELET POOLING: </li></ul><ul><li>- N- 1/3 RD of platelets sequestered in spleen, in hypersplenism this fraction increases </li></ul><ul><li>-splenectomy,embolic occlusion of splenic vasculature </li></ul><ul><li>- shunt surgeries in case of cirrhosis corrects platelet counts </li></ul><ul><li>MASSIVE BLOOD TRANSFUSION: </li></ul><ul><li>-replacement of pt blood volume in 24 hrs./ or &gt; 10 units of PCT </li></ul><ul><li>- platelet /FFP to supplemented in massive transfusions </li></ul>
  • 33. &nbsp;
  • 34. <ul><li>BERNARD SOULLIER SYNDROME </li></ul><ul><li>GLANZMAN’S THROMBASTHENIA </li></ul><ul><li>Gp 1b9 defect </li></ul><ul><li>adhesion to vesselwall impaired </li></ul><ul><li>to avoid trauma,antiplatelets </li></ul><ul><li>pl.transfusion </li></ul><ul><li>desmopressin </li></ul><ul><li>r factor 7a </li></ul><ul><li>antifibrinolytics </li></ul><ul><li>bonemarrow/stem cell tx </li></ul><ul><li>Gp 2b/3a defect </li></ul><ul><li>aggregation of platelets impaired </li></ul><ul><li>pl. transfusion </li></ul><ul><li>r factor 7a </li></ul><ul><li>antifibrinolytics </li></ul><ul><li>bonemarrow/stem cell tx </li></ul>
  • 35. <ul><li>URAEMIA: </li></ul><ul><li>-coagulopathy is an indication for dialysis </li></ul><ul><li>-erythropoietin </li></ul><ul><li>-cryo ppt </li></ul><ul><li>-blood transfusion </li></ul><ul><li>ANTI-PLATELET DRUGS: </li></ul><ul><li>---- withdraw offending drug </li></ul>
  • 36. &nbsp;
  • 37. <ul><li>-----principles </li></ul><ul><li>HEMOSTATIC LEVELS: </li></ul><ul><li>- lowest plasma conc. Of a given coagulation factor required for normal hemostasis </li></ul><ul><li>IN VIVO RECOVERY: </li></ul><ul><li>- after infusion of factors –loss from intra vascular space. </li></ul><ul><li>- adsorption of coagulation factors by platelets and various vascular surfaces </li></ul>
  • 38. <ul><li>phase 1: </li></ul><ul><li>-rapid loss of via diffusion </li></ul><ul><li>phase 2: </li></ul><ul><li>-biological half life </li></ul><ul><li>-determines frequency and dose </li></ul>
  • 39. <ul><li>FRESH FROZEN PLASMA: </li></ul><ul><li>-contain all coagulation factors , 5and 8 </li></ul><ul><li>slightly low </li></ul><ul><li>- thawed FFP used upto 5 days. </li></ul><ul><li>-ABO compatibility to be tested ,Rh neednot be tested </li></ul><ul><li>CRYOPRECIPITATE: </li></ul><ul><li>-contains fibrinogen,VWF,factor 8 and 9,fibronectin </li></ul><ul><li>-contains small amt of plasma </li></ul><ul><li>-ABO compatibility to be tested ,Rh neednot be tested </li></ul>
  • 40. <ul><li>PLATELETS: </li></ul><ul><li>-pooled random donors----upto 8 units can be pooled from different patients </li></ul><ul><li>-apherised platelet----from single donor </li></ul><ul><li>- lifespan after pooling -4 hrs ,unless properly stored. </li></ul><ul><li>- in emergencies ABO incompatibility can be compromised except for mild reactions . </li></ul>
  • 41. <ul><li>PURIFIED CONC. COAGULATION FACTORS: </li></ul><ul><li>RECOMBINANT FACTORS </li></ul><ul><li>PORCINE FACTORS </li></ul><ul><li>PROTHROMBIN COMPLEX CONCENTRATES: </li></ul><ul><li>- contains factor 2,7,9,10,protein c,s, </li></ul><ul><li>- high thrombogenic potential </li></ul>
  • 42. <ul><li>vasopressin analogues </li></ul><ul><li>releases VWF,factor 8 and 9 from vascular endothelial cells </li></ul><ul><li>also releases endothelium derived plasminogen activators ---causes fibrinolysis </li></ul><ul><li>so antifibrinolytics like EACA to be combined </li></ul><ul><li>repeated dosing causes depletion of sources of VWF. </li></ul><ul><li>used carefully in SHT,CCF. </li></ul>
  • 43. &nbsp;
  • 44. <ul><li>to avoid trauma, isometric exercises </li></ul><ul><li>to avoid anti-platelets </li></ul><ul><li>to avoid IM injections </li></ul><ul><li>caution regarding infections via blood products HIV,HEP B,C,prions,CMV. </li></ul><ul><li>therapy is complicated by development of inhibitors to clotting factors. </li></ul><ul><li>difficulty in treating these conditions. </li></ul>
  • 45. <ul><li>inherited factor 8 deficiency </li></ul><ul><li>depending on factor levels- </li></ul><ul><li>-severe &lt;1% </li></ul><ul><li>-moderate 1-5% </li></ul><ul><li>-mild 6-30% </li></ul><ul><li>mainstay of treatment to maintain hemostatic levels </li></ul><ul><li>dose required=(target levels-baseline levels)×body wt.in kg χ 0.5 </li></ul>
  • 46. <ul><li>----replacement therapy </li></ul><ul><li>mild bleeds,uncomplicated hemarthroses,superficial hematomas: </li></ul><ul><li>initial ---30-50% </li></ul><ul><li>maintenance --- 15-25% for 2-3 d </li></ul><ul><li>large hematomas,bleed into muscle: </li></ul><ul><li>&gt;50% for 1 wk </li></ul><ul><li>oropharyngealspaces, </li></ul><ul><li>retroperitoneum,CNS </li></ul><ul><li>bleeds : 50-100% for 7-10 days </li></ul><ul><li>surgical prophylaxis : 100% for 7-10 days </li></ul><ul><li>dental procedures : 50-100% for 3 days </li></ul>
  • 47. <ul><li>Other measures ….. </li></ul><ul><li>DDAVP : -0.3 µg/kg infused over 20 min </li></ul><ul><li>-nasal spray 150µg in each nostril </li></ul><ul><li>-2to3 fold rise in factor 8,with peak </li></ul><ul><li>at 30-60 min </li></ul><ul><li>Tranexamic acid : 25 mg/kg qid </li></ul><ul><li>EACA : loading dose -200 mg/kg </li></ul><ul><li>maintenance-100mg/kg every 6 hr. </li></ul>
  • 48. <ul><li>inherited deficiency of factor 9 </li></ul><ul><li>less frequent and less severe than hemophilia A </li></ul><ul><li>during replacement factor 9 has low in vitro survival , 30-50% </li></ul><ul><li>dose required =(target levels-baseline lines) χ body wt.in kg </li></ul><ul><li>therapy is complicated by inhibitor formation </li></ul><ul><li>DDAVP, EACA,tranexamic acid </li></ul>
  • 49. <ul><li>VWF stabilises factor 8, assists in platelet aggegation </li></ul><ul><li>VWD – types </li></ul><ul><li>1- partial defect </li></ul><ul><li>2-qualitative defect </li></ul><ul><li>3-severe quantitative defect </li></ul><ul><li>platelet type(pseudo) VWD- </li></ul><ul><li>defect in platelet GP 1b causing abnormal binding with VWD </li></ul>
  • 50. <ul><li>TYPE I : DDAVP (infusion/spray) </li></ul><ul><li>TYPE 2 A/B: </li></ul><ul><li>DDAVP+VWF containing factor 8 conc. </li></ul><ul><li>TYPE 2 M/N and TYPE 3: </li></ul><ul><li>- VWF containing factor 8 conc. </li></ul><ul><li>- prophylaxis is required only in TYPE3 </li></ul><ul><li>- replacement of factor 8 wont suffice as its half life is very low in the absence of VWF </li></ul>
  • 51. <ul><li>VWF REPLACEMENT: </li></ul><ul><li>50-80% -In major trauma,surgery,CNS bleeds </li></ul><ul><li>30-50%-minor surgery,dental procedures </li></ul><ul><li>peri partum bleeds </li></ul><ul><li>type 3 VWD patients develop antibodies against VWF </li></ul><ul><li>NON –REPLACEMENT THERAPY: </li></ul><ul><li>estrogen ,OCP </li></ul><ul><li>EACA </li></ul><ul><li>Tranexamic acid </li></ul>
  • 52. &nbsp;
  • 53. <ul><li>HEMORRHAGIC DISEASE OF NEW BORN: </li></ul><ul><li>- vitamin k 0.5 to 10 mg im to babies </li></ul><ul><li>-prophylactic administration of vit k </li></ul><ul><li>to mothers before delivery </li></ul><ul><li>MALABSORPTION OF VITAMIN K/ DRUGS: </li></ul><ul><li>-vitamin k 10mg im vit, </li></ul><ul><li>- coagulopathy reverts in 12-24 hrs. if not so there is a coexistent liver disease or DIC </li></ul>
  • 54. <ul><li>Thrombocytopenia </li></ul><ul><li>Decreased synthesis of coagulation factors </li></ul><ul><li>Increased fibrinolysis </li></ul><ul><li>----options are </li></ul><ul><li>Inj. Vitamin k </li></ul><ul><li>fresh frozen plasma </li></ul><ul><li>prothrombin complex concentrates </li></ul><ul><li>recombinant factor 7a </li></ul><ul><li>cryoprecipitate </li></ul>
  • 55. <ul><li>presents as coagulopathy in acute DIC and </li></ul><ul><li>Thrombotic complications in chronic DIC </li></ul><ul><li>-----management of DIC </li></ul><ul><li>stabilise the patient </li></ul><ul><li>treatment of the primary cause </li></ul><ul><li>platelet transfusion if &lt;20,000/cumm </li></ul><ul><li>fresh frozen plasma </li></ul><ul><li>packed cell transfusion </li></ul><ul><li>low molecular wt. heparin,antithrombin in chronic DIC </li></ul><ul><li>cryoppt .in hypofibrinogenemia. </li></ul>
  • 56. <ul><li>Recombinant activated protein C </li></ul><ul><li>– drotecogin alfa , inhibits activated factor 5 and 8. </li></ul><ul><li>tissue factor pathway inhibitor </li></ul><ul><li>recombinant -activated factor 7 </li></ul><ul><li>antiselectin antibodies – blocks platelet adhesion </li></ul><ul><li>IL 10 inhibitors (IL 10 s involved in coagulation cascade) </li></ul><ul><li>MAPK inhibitors (mitogen activated protein kinase involved in intracellular signalling in </li></ul><ul><li>inflammation. </li></ul>
  • 57. <ul><li>many patients develop allo-antibodies against clotting factors . </li></ul><ul><li>these antibodies acts as inhibitors of coagulation </li></ul><ul><li>common in hemophilia and very rare in other coagulation disorders </li></ul><ul><li>present in 5-10% of all hemophiliacs </li></ul><ul><li>20% of severe hemophilia A </li></ul><ul><li>3-5% of hemophilia B </li></ul>
  • 58. <ul><li>HIGH RISK GROUP: </li></ul><ul><li>severe deficiency of factor 8,9 </li></ul><ul><li>family history of inhibitors </li></ul><ul><li>african descents </li></ul><ul><li>mutations in factor 8 and factor 9 gene </li></ul><ul><li>--- there is a negative correlation with </li></ul><ul><li>HLA CW5 </li></ul>
  • 59. <ul><li>Plasma from normal individuals and pts are </li></ul><ul><li>mixed in 1:1 ratio----aPTT is prolonged in presence of inhibitors </li></ul><ul><li>BETHESDA ASSAY : detects specificity of inhibitors and its titre </li></ul><ul><li>one BETHESDA UNIT (BU) is the amount of antibody that neutralises 50% of factor 8 or 9 </li></ul><ul><li>in normal plasma after2 hr of incubation at 37’c </li></ul><ul><li>NIJMEGEN ASSAY :here pH of the system is controlled on 2 hrs of incubation </li></ul>
  • 60. <ul><li>high dose of clotting factors </li></ul><ul><li>recombinant factor 7a –which bypasses factor 8 step </li></ul><ul><li>prothrombin complex concentrates </li></ul><ul><li>IMMUNE TOLERANCE INDUCTION: </li></ul><ul><li>-based on daily infusion of the missing factor in small amounts until inhibitors disappears. </li></ul><ul><li>-it may take 1 yr. </li></ul><ul><li>RITUXIMAB </li></ul><ul><li>GENE THERAPY </li></ul><ul><li>LIVER TRANSPLANTATION </li></ul>
  • 61. &nbsp;
  • 62. &nbsp;
  • 63. <ul><li>osler-weber –rendu syndrome </li></ul><ul><li>screen for a-v malformations at cerebrum,pulmonary vessels,liver </li></ul><ul><li>in case of recurrent epistaxis – </li></ul><ul><li>laser therapy,arterial embolisation </li></ul><ul><li>pulmonary AVMs –embolotherapy </li></ul><ul><li>GI AVMs –endoscopic electrocautery </li></ul><ul><li>-laser </li></ul><ul><li>cerebral AVMs –steriotactic surgery </li></ul><ul><li>- radiosurgery </li></ul><ul><li>- embolotherapy </li></ul>
  • 64. <ul><li>EHLER-DANLOS SYNDROME </li></ul><ul><li>MARFAN SYNDROME </li></ul><ul><li>OSTEOGENESIS IMPERFECTA </li></ul><ul><li>PSEUDOXANTHOMA ELASTICUM </li></ul><ul><li>----To avoid contact sports,isometric exercises,antiplatelets </li></ul><ul><li>----to undergo regular screening </li></ul>
  • 65. <ul><li>pt can present with purpura,hematuria,hemoptysis etc </li></ul><ul><li>options : </li></ul><ul><li>- steroids </li></ul><ul><li>- plasmapheresis </li></ul><ul><li>- immunosuppresants </li></ul>
  • 66. &nbsp;
  • 67. &nbsp;
  • 68. <ul><li>Whether treatment should be withdrawn </li></ul><ul><li>abruptly or gradually withdrawn (&amp;quot;tailed off&amp;quot;) </li></ul><ul><li>is still debatable. </li></ul><ul><li>Theoretically, the &amp;quot; rebound hypercoagulability &amp;quot; which results from sudden discontinuation might predispose to rebound thrombosis. </li></ul><ul><li>Some clinicians tail off long term treatment over several weeks but withdrawal for short term treatment can be done suddenly. </li></ul>
  • 69. <ul><li>In life threatening hemorrhage: </li></ul><ul><li>- give inj.vit K-5-10 mg slow iv </li></ul><ul><li>- FFP,cryo </li></ul><ul><li>In minor bleeds-epistaxis,hematuria: </li></ul><ul><li>-give inj.vit 0.5-2mg iv </li></ul><ul><li>In asymptomatic individuals </li></ul><ul><li>INR : 3-6 reduce dose of OAC, repeat INR after 2 days </li></ul><ul><li>INR: &gt;6 oral vit K 2.5-5 mg </li></ul><ul><li>INR: &gt;18 warrants admission and reversal </li></ul>
  • 70. <ul><li>---- PROTAMINE SULFATE </li></ul><ul><li>protamine binds heparin to form a stable ion pair ,which is broken down by RES </li></ul><ul><li>DOSE: 1mg iv for every 100 IU of heparin </li></ul><ul><li>administered </li></ul><ul><li>in large doses ,protamine itself has some anticoagulant effect </li></ul>
  • 71. <ul><li>-- complications from thrombolytic therapy occur when patients receive higher dose per kg body wt. </li></ul><ul><li>--In that case </li></ul><ul><li>stop thrombolytic therapy </li></ul><ul><li>EACA : - 4-5g infusion in 1 hr----1g/hr </li></ul><ul><li>infusion over 8 hr. </li></ul><ul><li>- has intrinsic thrombogenic </li></ul><ul><li>potential </li></ul><ul><li>FFP/CRYOPPT. </li></ul><ul><li>APROTININ –banned by FDA. </li></ul>
  • 72. &nbsp;

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