HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING....

of 78 /78
HEMORRHAGIC DIATHESIS

Embed Size (px)

Transcript of HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING....

  • HEMORRHAGIC DIATHESIS

  • HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY, PLATELET DISORDER (THROMBOCYTOPENIA AND THROMBOCYTOPATHY) AND VASOPATHY. EACH TYPE IS SUBDIVIDED INTO CONGENITAL AND ACQUIRED.

  • Petechial-ecchymosisHematomaMixed (Petechia & Hematoma)VasculaticAngiomatosicThe main bleeding types

  • THE MAIN BLEEDING SICKNESS TYPESHematomic (massive, deep, painful; bleeding may occur anywhere. The most common sites of bleeding are into joints (knees, ankles, elbows), into muscles, from the gastrointestinal tract, cause of the bleeding can be intramuscular injection; characterized by early postoperative & posttraumatic bleeding)

  • hematoma

  • petechia-spotted (macula)

  • MACULA-HEMATOMA

  • VASCULITIC PURPURA

  • ANGIOMA

  • THE MAIN COAGULOGRAM INDEXES

    1IndexHypocoagulationNormocoagulationHypercoagulationBleeding time (by Lee-White methods), min>55-3< 3Platelets number320Platelet adhesiveness45Time of plasma recalcification, sec>120120-601111-8

  • SCREENING TESTS FOR BLEEDING DISORDERS

    TestAbnormality detectedBlood count and filmAnaemia, leukaemia, disseminatedintravascular coagulationPlatelet countThrombocytopeniaActivated partial thromboplastin timeDeficiency of all coagulation factorsexcept VII, especially follows VIII and IX;heparinProthrombin timeDeficiency of factors I, II, V, VII, and X;warfarinThrombin time or fibrinogenHypofibrinogenaemia or dysfibrinogenaemia; heparin; fibrin degradation productsBleeding time Test of platelet-vessel wall interaction

  • COAGULOPATHYI. Congenital Deficiency of coagulation factor VIII (hemophilia A) Deficiency of coagulation factor IX (hemophilia B) Deficiency of coagulation factor XI (hemophilia C) Deficiency of other coagulation factors (I, II, V, VII, IX, X and XIII) Deficiency of XII factor, prekallikrein or kininogen, protein C and S (without excessive bleeding) von Willebrands disease (angiohemophilia)

  • COAGULOPATHYII. Acquired1) Hypoprothrombinemia Deficiency of vitamin K due to acholia of GIT (in cholestatic jaundice) In overdose of indirect anticoagulant (antagonist of vitamin K) In liver cirrhosis (due to reduced protein production)2) Consumption of coagulation factors (II stage of DIC)3) Heparin overdose4) Activation of fibrinolytic system In administration of streptokinase etc. In trauma, obstetrical or surgical operations In malignant neoplasms In shock, sepsis, hematological malignancies, III stage of DIC

  • PLATELET DISORDERS

    ThrombocytopathyI. Congenital (deficiency of platelet membrane glycoprotein) Glanzmann's ThrombastheniaII. Acquired (normal platelet count in blood and bone marrow but its functions are decreased) Drugs (after intake of antiplatelet agents: aspirin, Ticlide); Immune, toxic, septic processes; Hematological malignancies and anemiasThrombocytopenia (decrease in the number of platelets)I. Werlhofs disease - autoimmune thrombocytopenic purpuraII. Symptomatic Immune (heteroimmune, isoimmune,) Toxic (in phosphorus poisoning etc.) Methaplastic (in hematological malignancies or myelocarcinosis) Drug-induced (cytostatics)

  • THROMBOCYTOPENIAThrombocytopenia (decrease in the number of platelets) - Idiopathic thrombocytopenic purpura (ITP) - Thombotic thrombocytopenic purpura (TTP) - Heparin-induced thrombocytopenia (HIT)- Hemolytic-Uremic Syndrome- Chronic liver disease

  • VASOPATHY

    I. Congenital Telangiectasiae (Rendu-Osler-Weber disease) Aneurysm of fine vessels Ehlers-Danlos syndrome, Marfans syndrome, retinocerebral angiomatosis (von Hippel-Lindau syndrome), encephalotrigeminal angiomatosis (Sturge-Kalisher-Weber syndrome)II. Acquired Hemorrhagic vasculitis Henoch-Schnlein purpura Immune vasculitis Systemic vasculitis Avitaminosis of vitamin C

  • THE CLOTTING MECHANISMINTRINSIC EXTRINSICPROTHROMBIN THROMBINFIBRINOGENFIBRIN(II)(III)(I)VXTissue ThromboplastinCollagenVIIXIIXIIXVIII

  • COAGULATION PATHWAYTwo pathways for fibrin clot formation:IntrinsicInitiated by negatively charged surfaceExtrinsicInitiated on tissue injuryBoth pathways converge on a final common pathwayProthrombin Thrombin (Most critical step )Fibrinogen Fibrin ClotThe pathways are complex and involve many different proteins (called blood clotting factors)

  • COAGULATION CASCADE - CONTINUEDControl of coagulation Antithrombins (e.g., antithrombin III)Proteins C and SFibrinolytic cascade Plasminogen plasmin fibrin break down products (*FDP or FSP) d-dimer is most important of the FDPs*FDP / FSP Fibrin degradation products / Fibrin split products

  • CLOTTING FACTOR ABNORMALITIESCongenital disordersVon Willebrand disease MC with minimal bleedingFactor VIII Deficiency - Hemophilia A or Classic TypeFactor IX Deficiency Hemophilia BAcquired disordersVit. K deficiency Oral anti-coagulantsCoumarin derivatives = warfarin inhibit Vit. K factors Liver diseases synthesis of factors

  • www.themegallery.comCompany Logofactor IX deficiencyfactor VIII deficiencyfactor XI deficiencyHaemophilia

  • FORMS Haemophilia A - factor VIII deficiency, "classic haemophilia" (X-linked) Haemophilia B - factor IX deficiency, "Christmas disease" (X-linked) Haemophilia C - factor XI deficiency (Ashkenazi Jews, autosomal recessive) The unrelated type 1 and type 2 von Willebrand disease (vWD)

  • Company LogoF VIII C level 5-25 %Classification (F VIII C level)

  • CLINICAL SEVERITY OF HAEMOPHILIA A AND B

    Factor value*Bleeding tendency

    Less than 0.02Severe - frequent spontaneous bleeding into joints, muscles, and internal organs0.02-0.05Moderatesome spontaneous bleeds,bleeding after minor traumaMore than 0.05Mildbleeding only after significant trauma orsurgery* Normal value of factors VIII and IX is 0.5-1.5

  • HEMOPHILIA AMC hereditary disease with serious bleedingX-linked recessiveIn 30% No family history (new mutations)15% of severe cases develop factor VIII inhibitors amount or activity of factor VIIIfactor VIII = cofactor for activation of factor X in the coagulation cascadeSymptoms usually hemoarthrosis, bruising, hemorrhage after trauma or surgery

  • SIGNS & SYMPTOMS Symptoms of hemophilia are usually first noticed during infancy or childhood. However, some people with milder forms of hemophilia may not develop symptoms until later on. The following are signs of hemophilia that may be noticed shortly after birth: Bleeding into the muscle, resulting in a deep bruise after receiving a routine vitamin K shot. Prolonged bleeding after a male child is circumcised. Other symptoms of hemophilia include: Bleeding into a joint or muscle that causes pain and swelling. Abnormal bleeding after an injury. Easy bruising. Frequent nosebleeds. Blood in the urine (hematuria). The most common bleeding problem a person with severe hemophilia has is bleeding into a joint (hemarthrosis), often without an injury.

  • Arhtropathy Hematomic bleeding sickness typesDiagnostic criteriaHemophilia

  • BIOCHEMICAL ASPECTS:Factor VIII circulates in the plasma as a complex of factor VIII and von Willebrand factor. The molecular weight of human factor VIII has been estimated to be 285,000. Hemophelia A in which factor VIII (antihemophelic factor) is either absent or dysfunctional is transmitted by X chromosomal inheritance. Hemophelia A is at least four times more common than hemophelia B.

  • DIAGNOSTIC CRITERIAFamily_history_of_coagulation_disorders: positive APTT:abnormal Mixing_APTT:corrected Factor_VIII:C_activity:abnormal

  • ConditionProthrombin timePartial thromboplastin timeBleeding timePlatelet countVitamin K deficiency or warfarinprolongednormal or mildly prolongedunaffectedunaffectedDisseminated intravascular coagulationprolongedprolongedprolongeddecreasedvon Willebrand diseaseunaffectedprolongedprolongedunaffectedHemophiliaunaffectedprolongedunaffectedunaffectedAspirinunaffectedunaffectedprolongedunaffectedThrombocytopeniaunaffectedunaffectedprolongeddecreasedUremiaunaffectedunaffectedprolongedunaffectedGlanzmann's thrombastheniaunaffectedunaffectedprolongedunaffectedBernard-Soulier syndromeunaffectedunaffectedprolongeddecreased or unaffected

  • TREATMENTIn mild bleeding: 1-desamino-8-D-arginine vasopressin (DDAVP). The level of factor VIII must be maintained at least 30%. In non-life-threatening bleeding or pre-op: factor VIII concentrates. The minimal hemostatic level of factor VIII:C in this case is 50%. Central nervous system hemorrhage and severe bleeding: factor VIII concentrates. The level of factor VIII:C must be maintained at 80% - 100%. Each unit of factor VIII concentrates will raise the level of factor VIII by 2%/kg of body weight. Adjunctive therapy in dental surgery for mild and moderate hemophelia A: epsilon-aminocaproic acid (EACA). Avoidance of aspirin-containing compounds. For monitoring therapy, factor VIII assay is the test of choice. Dosage: the (activity ) units of factor VIII required can be calculated from: 40*BW*(desired factor level-actual factor level)/100 where BW is body weight in kg

  • TREATMENTThe dose of factor VIII concentrate is calculated assuming that one unit of factor VIII is the amount present in 1 mL of plasma. Plasma volume is 40 mL/kg, and the volume of distribution of factor VIII:C is 1.5 times the plasma volume. Thus, to raise the level 100%, the dose should be 40 x 1.5 = 60 units/kg, or approximately 4000 units for a 70-kg individual. To raise the levels to 25% would require 1000 units. The half-life of factor VIII:C is approximately 12 hours. Thus, during major surgery, to achieve an initial level of 100% and maintain it continuously at greater than 50%, a dose of 60 units/kg (approximately 4000 units) initially followed by 30 units/kg (approximately 2000 units) every 12 hours should be adequate. During surgery, initially verify that these doses give the anticipated factor VIII levels. If factor VIII levels fail to rise as expected, an inhibitor should be suspected.

  • HEMOPHILIA BDEFICIENCY OF FACTOR IXFactor IX deficiencyX-linked recessiveMuch less commonClinically= indistinguishable from Hemophilia A with Similar lab findingsDiagnosis by factor IX levelsTreat with recombinant IX

  • DIAGNOSTIC CRITERIAFamily_history_of_coagulation_disorders:positive Mixing_APTT:corrected Factor_IX_assay:abnormalAPTT:abnormal

  • TREATMENTFor patients with mild form of factor IX deficiency with non-life-threatening bleeding, the treatment of choice is FFP. For the severe form of hemophelia B or in life- threatening situation, prothrombin complex concentrates are the treatment of choice.

  • TREATMENTTarget levels of factor IX for therapy: Severe hemorrhage: 20% - 50% for 3-5 days, then 10% - 20% for the next 10 days. Minor hemorrhage: 20% for 7 days. Surgery: 50% - 70% for 2 days, then 30% - 40% for 3 days, then 20% for 7 days.

  • TREATMENTDosage: the (activity) units of factor IX required can be calculated from: 80*BW*(desired factor level-actual factor level)/100 where BW is body weight in kg Note that in-vivo recovery of factor IX is about 50%.

  • Company LogoMildHemophilia A Treatment (cryoprecipitate)

  • VON WILLEBRAND'S DISEASEEssentials of DiagnosisFamily history with autosomal dominant pattern of inheritance. Prolonged bleeding time, either at baseline or after challenge with aspirin. Reduced levels of factor VIII antigen or ristocetin cofactor. Reduced levels of factor VIII coagulant activity in some patients. Symptoms and Signsvon Willebrand's disease is a common disorder affecting both men and women. Most cases are mild. Most bleeding is mucosal (epistaxis, gingival bleeding, menorrhagia), but gastrointestinal bleeding may occur. In most cases, incisional bleeding occurs after surgery or dental extractions. von Willebrand's disease is rarely as severe as hemophilia, and spontaneous hemarthroses do not occur (except in the rare type III). The bleeding tendency is exacerbated by aspirin. Characteristically, bleeding decreases during pregnancy or estrogen use.

  • THE MAIN BLEEDING SICKNESS TYPESMixed (Petechial & Hematomic) (combined features of both types, but there are some difference: in contrast to hematomic - bleeding are into joints very rare, mostly it is located in subcutaneous, retroperitoneal, mesenteric, subserous intestinal layer or into internal organ);in contrast to petechial-ecchymosic bleeding - hemorrhagic syndrome characterized by large bruise)

  • TREATMENT

    The bleeding disorder is characteristically mild, and no treatment is routinely given other than avoidance of aspirin. However, patients often need to be prepared for surgical or dental procedures. The bleeding time is probably the best indicator of the likelihood of bleeding, and prophylactic therapy may be reasonably withheld if the procedure is minor and the bleeding time is normal.Desmopressin acetate (DDAVP) is useful for mild type I von Willebrand's disease and should be considered first. The dose is 0.3 mcg/kg, after which vWF levels usually rise two- to threefold in 3090 minutes. It can also be given as a nasal spray; levels peak 2 hours after use. The antifibrinolytic agent aminocaproic acid (EACA) is useful as adjunctive therapy during dental procedures.

  • PLATELET HEMOSTATIC ACTIVITY1. Pl stimulate vasoconstriction of injured vessels2. Pl form hemostatic plug (platelet adhesion) + platelet aggregation to seal small vessel wall3. Pl play role in fibrin clot formation

  • THROMBOCYTOPENIA

    Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood.Generally speaking a normal platelet count ranges from 180,000 and 320,000 per mm3. Signs and symptomsOften, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine full blood count. Occasionally, there may be bruising, nosebleeds and/or bleeding gums.It is vital that a full medical history is elicited, to ensure the low platelet count is not due to a secondary process. It is also important to ensure that the other blood cell types red blood cells, and white blood cells, are not also suppressed.

  • THROMBOCYTOPENIAPetechial-ecchymosicDiagnostic criteriaDeacrease of platelets

  • PLATELET DISORDERSThrombocytopenia = Reduced platelet numberCauses Decreased production of plateletsvitamin B12 or folic acid deficiencyDecreased platelet survivalImmunologic or Nonimmunologic etiologySequestration- Hypersplenism ameliorated by splenectomyDilutionalMassive transfusions

  • IMMUNE THROMBOCYTOPENIC PURPURA (ITP) CauseAntiplatelet antibodies Antigen - platelet membrane glycoprotein complexes IIb-IIIa and Ib-IXMorphologyPeripheral Bloodthrombocytopenia, abnormally large platelets (megathrombocytes or Giant platelets),MarrowNormal or Increased magakaryocyte #Diagnosis - by exclusionBleeding time - prolonged, but PT & PTT - normal Marrow magakaryocyte # - your Diagnosis of ITP is ?????

  • NECESSARY EVALUATION History: Isolated bleeding symptoms consistent withthrombocytopenia without constitutional symptoms(e.g. significant weight loss, bone pain, night sweats). Physical examination: Bleeding symptoms in the absence of hepatosplenomegaly, lymphadenopathy, or stigmata of congenital conditions.

  • NECESSARY EVALUATION Complete blood count: Isolated thrombocytopenia (platelet count
  • BONE MARROW EVALUATION Bone marrow examination is unnecessary in patients with the typical features of ITP outlined above, irrespective of the age of the patient. Bone marrow examination is felt to be unnecessary in children with typical ITP prior to initiation of treatment with corticosteroids, prior to splenectomy, or in patients who fail intravenous immunoglobulin (IVIg) therapy.

  • BONE MARROW EVALUATION The presence of abnormalities in the history, physical examination, or the complete blood count and peripheral blood smear should be further investigated, e.g. with a bone marrow examination or other appropriate investigations, before the diagnosis of ITP is made.

  • ADDITIONAL EVALUATIONS All adult patients with newly diagnosed ITP should undergo testing for HIV and HCV. There is insufficient evidence to support the routine use of anti-platelet, antiphospholipid, and anti-nuclear antibodies, thrombopoietin levels, or platelet parameters obtained on automated analyzers in the evaluation of patients with suspected ITP.

  • DIAGNOSTIC CRITERIA:Plt_count:abnormal (low) Peripheral blood smear:no increase in schistocytes Bone_marrow:megakaryocytosis

  • THE MAIN BLEEDING SICKNESS TYPESPetechia-ecchymosis (is usually localized to superficial sites such as the skin and mucous membranes, wich often combined with menorrhagia, nose bleeding, gumms bleeding; rare with gastrointestinal bleeding or brain hemorrhage; it is small, painless, provoked by simple action like skin cleaning, measure of blood pressure etc; pinch test is positive)

  • ITP

    FeatureAcuteChronicAge / SexChildrenAdult/FemaleOnsetAbruptGradualPredisposing FactorsViral infection/ vaccine-Duration6mnothsPathogenesis-IgG against Platelet GPPeripheral smearThrombocytopenia & Giant PLTSSameBone marrowNormal or MegakaryocytesSame

  • ITP

    FeatureAcuteChronicTestsProlonged BT & Normal PT & PTTSameComplication (most dangerous)Intracranial bleedSameClinical courseSpontaneous remissionNoTreatment PLT. Transfusion Splenectomy If

  • ConditionProthrombin timePartial thromboplastin timeBleeding timePlatelet countVitamin K deficiency or warfarinprolongednormal or mildly prolongedunaffectedunaffectedDisseminated intravascular coagulationprolongedprolongedprolongeddecreasedvon Willebrand diseaseunaffectedprolongedprolongedunaffectedHemophiliaunaffectedprolongedunaffectedunaffectedAspirinunaffectedunaffectedprolongedunaffectedThrombocytopeniaunaffectedunaffectedprolongeddecreasedUremiaunaffectedunaffectedprolongedunaffectedGlanzmann's thrombastheniaunaffectedunaffectedprolongedunaffectedBernard-Soulier syndromeunaffectedunaffectedprolongeddecreased or unaffected

  • MANAGEMENTOF ITPThe goal of all treatment strategies for ITP is to achieve a platelet count that is associated with adequate hemostasis, rather than a normal platelet count. The decision to treat should involve a discussion with the patient and consideration of the severity of bleeding, anticipated surgical procedures, medication side effects, and health-related quality of life.

  • INITIAL MANAGEMENT OF ITPAssessment of Disease Status: What bleeding is the patient experiencing? Determine the timing, location, and severity ofbleeding symptoms. Does this patient have any additional risk factors for bleeding such as use of antithrombotic agents or high-risk occupation? Is a surgical procedure anticipated? Is this patient likely to comply with recommended treatments? Is the bleeding experienced by this patient interfering with his or her daily activities or causing significant anxiety?

  • GENERAL CONSIDERATIONS FOR INITIAL MANAGEMENT The majority of patients with no bleeding or mild bleeding (defined here as skin manifestations only, such as petechiae and bruising) can be treated with observation alone regardless of platelet count. First-line treatment includes observation, corticosteroids, IVIg, or anti-D immunoglobulin (anti-D). Anti-D should be used with caution given recent FDA warnings of severe hemolysis. It is therefore not advised in patients with bleeding causing a decline in hemoglobin, or those with evidence of autoimmune hemolysis.

  • DRUG INDUCED THROMBOCYTOPENIAHEPARIN INDUCED THROMBOCYTOPENIA (HIT)Seen in 3-5% of patients treated with unfractionated heparin thrombocytopenic after 1-2 weeks of RxCaused by IgG antibodies against platelet factor 4/heparin complexes on platelet surfaces Exacerbates thrombosis, both arterial and venous (in setting of severe thrombocytopenia) Antibody binding results in platelet activation and aggregation.Rx - cessation of heparinOther drugs???

  • PLATELET FUNCTIONAL DISORDERS

  • VASCULAR ABNORMALITIESCausesInfectionsMeningococcemia, Rickettsioses , Infective endocarditisDrug reactions Hereditary hemorrhagic telangiectasia Autosomal dominant Cushing syndromeHenoch - Schnlein Purpura systemic hypersensitivity disease of unknown cause polyarthralgia, and acute Glomerulonephritis Palpable purpuric rash, colicky abdominal pain Scurvy and the Ehlers-Danlos syndromeAmyloid infiltration of blood vessels

  • THE MAIN BLEEDING SICKNESS TYPESVasculatic (hemorrhage due to inflammatory changes of small vessels, the main cause are immune disorders or infectious agent)

  • THE MAIN BLEEDING SICKNESS TYPESAngiomatosic (hemorrhage due to vascular dysplasia, teleangiectasia; the main clinical criteria is relapsing bleeding without hemorrhage in skin, subcutaneous and other tissue; nose bleeding are most often, dangerous and massive)

  • Thank you for attention!