BLEEDINGBLEEDINGDISORDERDISORDERProf. Rafi Ahmed GhoriProf. Rafi Ahmed GhoriFCPSFCPSLIAQUAT UNIVERSITY OFLIAQUAT UNIVERSITY OFMEDICAL & HEALTH SCIENCESMEDICAL & HEALTH SCIENCESJAMSHOROJAMSHORO
BLEEDING DISORDERBLEEDING DISORDER• Definition:Definition:• Disorder characterized by spontaneous/Disorder characterized by spontaneous/excessive bleeding following trauma.excessive bleeding following trauma.• Etiology:Etiology:• A.VESSEL WALL ABNORMALITIES:A.VESSEL WALL ABNORMALITIES:• Vessel wall abnormalities may beVessel wall abnormalities may becongenital OR acquired i-e vasculitiscongenital OR acquired i-e vasculitismay result in purpuric lesions.may result in purpuric lesions.
HERIDITARY HEOMORRAGICHERIDITARY HEOMORRAGICTELANGECTSIASIS:TELANGECTSIASIS:• Dominant inherited condition. There is aDominant inherited condition. There is atelengectiasis and small aneurysms found ontelengectiasis and small aneurysms found onfinger tips, face, nasal passages, tongue andfinger tips, face, nasal passages, tongue andGIT.GIT.• Small group of people develop pulmonary A/V :Small group of people develop pulmonary A/V :anemia due to occult GIT bleeding.anemia due to occult GIT bleeding.• Rx.Rx.• Iron therapy for blood loss.Iron therapy for blood loss.• Local cautery/laser therapy for single lesion fromLocal cautery/laser therapy for single lesion frombleeding (epistaxis).bleeding (epistaxis).• Estrogens may be tried.Estrogens may be tried.
EHLERS DANLOS DISEASE:EHLERS DANLOS DISEASE:• Congenital disorder of collagen synthesisCongenital disorder of collagen synthesisin which capillaries are poorly supportedin which capillaries are poorly supportedby s/c collagen and ecchymosis areby s/c collagen and ecchymosis arecommonly observed.commonly observed.
B.PLATELETS FUNCTIONALB.PLATELETS FUNCTIONALDISORDER:DISORDER:• Thrombocytopenia (quantitative plateletsThrombocytopenia (quantitative plateletsdysfunction)dysfunction)• S/S:S/S:– Dominated clinically by petechialDominated clinically by petechialcutaneous bleeding, intracranialcutaneous bleeding, intracranialbleeding and arising from mucusbleeding and arising from mucusmembrane/surface.membrane/surface.• Characterized by decreased plateletsCharacterized by decreased plateletscount and prolong bleeding timecount and prolong bleeding time
Management:Management:• Underlying causeUnderlying cause• Platelet transfusionPlatelet transfusionMechanism of Thrombocytopenia:Mechanism of Thrombocytopenia:• Failure of megakaryocytic maturation.Failure of megakaryocytic maturation.• Excessive platelets consumption afterExcessive platelets consumption aftertheir release into circulation i-e ITP, DICtheir release into circulation i-e ITP, DICetc.etc.• Platelets sequestration in enlargedPlatelets sequestration in enlargedspleen i-e HYPERSPLEENISMspleen i-e HYPERSPLEENISM
IDIOPATHIC THROMBOTICIDIOPATHIC THROMBOTICTHROMBOCYTOPENICTHROMBOCYTOPENICPURPURA.PURPURA.• Autoimmune antibody IgG is formed againstAutoimmune antibody IgG is formed againstunknown antigen of platelets membrane/surface.unknown antigen of platelets membrane/surface.• Antipletelet antibody binds to complement,Antipletelet antibody binds to complement,platelets are not destroyed by direct lysis.platelets are not destroyed by direct lysis.• Rather destruction takes place in spleen, whereRather destruction takes place in spleen, wherespleenic macrophages with Fc bind to antibodyspleenic macrophages with Fc bind to antibodycoated platelets.coated platelets.
Clinical Features:Clinical Features:In Children:In Children:• Commonly occur in children, often precipitatedCommonly occur in children, often precipitatedby viral infection and usually self limitedby viral infection and usually self limited• Pt is systematically well and not febrile.Pt is systematically well and not febrile.• Present e-c/o mucosal/skin bleeding,Present e-c/o mucosal/skin bleeding,mennorrhagia, purpura, petechiae.mennorrhagia, purpura, petechiae.
• Adults:Adults:• Commonly effects female.Commonly effects female.• Ratio 2:1 (male/female ratio)Ratio 2:1 (male/female ratio)• Peak incidence 20-50 years of age.Peak incidence 20-50 years of age.• Δ LAB:Δ LAB:• Hallmark of disease is thrombocytopenia i-eHallmark of disease is thrombocytopenia i-eplatelets below 10,000 /ml.platelets below 10,000 /ml.• Bone marrow will appear normal.Bone marrow will appear normal.
RxRx• PREDENISONONE:PREDENISONONE: 1-2 mg/kg/day.1-2 mg/kg/day.• SPLEEN ECTOMY: immunoglobulin 1g/kg/daySPLEEN ECTOMY: immunoglobulin 1g/kg/day2-3 days.2-3 days.• DANAZOLE:DANAZOLE:600mg/day response rate is600mg/day response rate is50%50%• IMMUNOSUPPERESSIVE DRUGS: i-eIMMUNOSUPPERESSIVE DRUGS: i-evincristine, vinblastine, azathioprine,vincristine, vinblastine, azathioprine,cyclosprin, cyclophosphomide.cyclosprin, cyclophosphomide.• Prognosis:Prognosis:• The prognosis for remission is good. Disease isThe prognosis for remission is good. Disease isinitially controlled with prednisolone,initially controlled with prednisolone,spleenectomy is definite Rx.spleenectomy is definite Rx.
TIP:TIP:THROMBOTICTHROMBOTICTHROMBOCYTOPENIC PURPURA:THROMBOCYTOPENIC PURPURA:Def:Def:• TIP is an uncommon syndrome withTIP is an uncommon syndrome withmicroangiopathic hemolytic anemia,microangiopathic hemolytic anemia,thrombocytopenia and markedly increased LDH,thrombocytopenia and markedly increased LDH,Non-infectious fever, Neurologic disorder, renalNon-infectious fever, Neurologic disorder, renalabnormalities are less commonly seen.abnormalities are less commonly seen.• Pathogenesis may be diff: of von Willibrand’sPathogenesis may be diff: of von Willibrand’sdisease factors clearing protease, in some casedisease factors clearing protease, in some caseantibody directed against protease.antibody directed against protease.
Clinical features:Clinical features:• Primarily in young aged 20-25 yr, slightlyPrimarily in young aged 20-25 yr, slightlycommon in female.common in female.• Pts present with anemia, bleeding, feverPts present with anemia, bleeding, feverand neurological manifestation.and neurological manifestation.• Neurological symptoms may be, headNeurological symptoms may be, headache, confusion aphasia, alteration inache, confusion aphasia, alteration inconsciousness from lethargy to comeconsciousness from lethargy to comewith more advanced one may see hemiwith more advanced one may see hemiparesis + seizures.paresis + seizures.
LAB:LAB:• Anemia, reticulocytosis and occasionalAnemia, reticulocytosis and occasionalcirculating nucleated cells.circulating nucleated cells.• Hallmark microangiopathic picture withHallmark microangiopathic picture withfragmented RBC’s i-e (schistocytes, helmetfragmented RBC’s i-e (schistocytes, helmetcells, triangle forms) on smear.cells, triangle forms) on smear.• Thrombocytopenia invariably present.Thrombocytopenia invariably present.• Hemolysis may be manifested with increasedHemolysis may be manifested with increasedindirect bilirubin, hemoglobinemia, methemindirect bilirubin, hemoglobinemia, methemalbuminia which impart a brown colour toalbuminia which impart a brown colour toplasma.plasma.• LDH markedly increased.LDH markedly increased.• Coomb’s test –ve.Coomb’s test –ve.• Coagulation test: PT, APPTT, fibrinogenCoagulation test: PT, APPTT, fibrinogenNormal, (fibrin degradation product) FDP mayNormal, (fibrin degradation product) FDP maybe elevatedbe elevated..
• Rx:Rx:• Plasmapheresis with /without prednisone antiPlasmapheresis with /without prednisone antiplatelets aspirin 325 mg/daily , dipyridamole 75platelets aspirin 325 mg/daily , dipyridamole 75mg × TDS may be given.mg × TDS may be given.• Combination spleenectomy, steroids andCombination spleenectomy, steroids anddextran may be used with success.dextran may be used with success.• Immuno suppressive therapy i-eImmuno suppressive therapy i-e(cyclophosphomide(cyclophosphomide ).).• Prognosis:Prognosis:• 80-90 % Pts recover completely with plasma80-90 % Pts recover completely with plasmapharesis while 20% pts will be chronic andpharesis while 20% pts will be chronic andrelapsing.relapsing.
B.QUALITATIVE PLETELETB.QUALITATIVE PLETELETDISORDERDISORDER::CONGENITAL:CONGENITAL:• Glansmann’s thrombostheniaGlansmann’s thrombosthenia• Bernard souliar syndromeBernard souliar syndrome• Storage pool diseaseStorage pool diseaseACQUIREDACQUIRED• Myeloproliferative disorder.Myeloproliferative disorder.• UremiaUremia• Drugs i-e NSAIDS AspirinDrugs i-e NSAIDS Aspirin• AutoantibodyAutoantibody• ParaprotiensParaprotiens• Acquired storage pool diseaseAcquired storage pool disease• Fibrin degradation productsFibrin degradation products• Von Willibrand’s diseaseVon Willibrand’s disease
BERNARD SOULIER SYNDROME:BERNARD SOULIER SYNDROME:• Bare Autosomal recessive intrinsic plateletsBare Autosomal recessive intrinsic plateletsdisorder.disorder.• Occurs due to lack of glycoprotein (41 b)Occurs due to lack of glycoprotein (41 b)receptor for von Willibrand’s factor whichreceptor for von Willibrand’s factor whichmediates platelets adhesions to submediates platelets adhesions to subendothelium.endothelium.• Clinical Features:Clinical Features:• Presents with mucosal bleeding and postPresents with mucosal bleeding and postoperatively as well.operatively as well.• LAB:LAB:• Thrombocytopenia may be present, andThrombocytopenia may be present, andabnormally large.abnormally large.• BT is prolongedBT is prolonged• Von Willibrand’s factor NormalVon Willibrand’s factor Normal• Rx:Rx:
GLANSMANN’sGLANSMANN’sTHROMBASTHENIA:THROMBASTHENIA:• Rae Autosomal recessive disorder.Rae Autosomal recessive disorder.• Platelets unable to aggregate b/c lack ofPlatelets unable to aggregate b/c lack ofreceptors (containing glycoprotein II b + III a)receptors (containing glycoprotein II b + III a)for fibrinogen which bridges b/w the plateletsfor fibrinogen which bridges b/w the plateletsduring aggregation.during aggregation.• Clinical Features:Clinical Features:• Mucosal bleedingMucosal bleeding• LAB:LAB:• Platelets no’s and morphology are normalPlatelets no’s and morphology are normal• B.T is prolongedB.T is prolonged• Platelets fails to aggregate in respond to typicalPlatelets fails to aggregate in respond to typicalagainst (ADP, collagen, thrombin) butagainst (ADP, collagen, thrombin) butaggregate in respond to risocetin by separateaggregate in respond to risocetin by separatemechanismmechanism• RxRx::• Platelet transfusionPlatelet transfusion
VON-WILLIBRAND’SVON-WILLIBRAND’SDISEASE:DISEASE:• It’s a transmitted by Autosomal dominant andIt’s a transmitted by Autosomal dominant andgene for (VWF) is located on chromosome 12gene for (VWF) is located on chromosome 12• VWF is synthesized by endothelial cells andVWF is synthesized by endothelial cells andmegakaryocytic that performs two functionsmegakaryocytic that performs two functions– It acts as carrier protein for factor VIII whichIt acts as carrier protein for factor VIII whichit is non-covalently bound. A deff: thereforeit is non-covalently bound. A deff: thereforeleads to decreased plasma factor VIII level.leads to decreased plasma factor VIII level.– It form bridges b/w platelets and subIt form bridges b/w platelets and subendothelium eg collagen allowing platelets toendothelium eg collagen allowing platelets toadhere to damaged vessel walls. There foreadhere to damaged vessel walls. There foredecreased diff: of VWF leads to prolongdecreased diff: of VWF leads to prolongbleeding after minor trauma.bleeding after minor trauma.
• Clinical Features:Clinical Features:• Mucosal bleeding as already discussed.Mucosal bleeding as already discussed.• LAB:LAB:• Reduced level of VWF which of lienReduced level of VWF which of lienaccomplished by sec: reduction in factor VIIIaccomplished by sec: reduction in factor VIIIand prolonged bleeding time (B.T)and prolonged bleeding time (B.T)• Rx:Rx:• MILD HAEMORRHAGES:MILD HAEMORRHAGES:• Desmopressin 0.3 μg/kg, after which VWFDesmopressin 0.3 μg/kg, after which VWFlevels usually raise 3 in 30-90 minuteslevels usually raise 3 in 30-90 minutes• MASSIVE HAEMORRHAGES:MASSIVE HAEMORRHAGES:• Factor VIIIFactor VIII
C. COAGULATION DISORDER:C. COAGULATION DISORDER:• Coagulation factor disorder can either canCoagulation factor disorder can either caneither arise from single factor usuallyeither arise from single factor usually“congenital deficiency” eg factor VIII resulting“congenital deficiency” eg factor VIII resultingin HAEMOPHILCIA-A or multiple factor which isin HAEMOPHILCIA-A or multiple factor which isacquired eg Sec: to liver disease or warfarinacquired eg Sec: to liver disease or warfarintherapy.therapy.
CONGENITAL BLEEDINGCONGENITAL BLEEDINGDISORDER:DISORDER:• HAEMOPHILIAHAEMOPHILIA• It is hereditary disease affecting malesIt is hereditary disease affecting malesbut transmitted by females andbut transmitted by females andcharacterized by prolong coagulation andcharacterized by prolong coagulation andlife long tendency to excessivelife long tendency to excessivehemorrhagehemorrhage• HEAMOPHILIA – A CLASSIC TRUEHEAMOPHILIA – A CLASSIC TRUEHAEMOPHILIAHAEMOPHILIA• X-linked disorderX-linked disorder• Due deff: of factor VIIIDue deff: of factor VIII
• C/F:C/F:• Although it is congenital disorder bleedingAlthough it is congenital disorder bleedingoccurs as bruising when babies are about 6occurs as bruising when babies are about 6month old when they begin to move about,month old when they begin to move about,trauma results in excessively bleeding.trauma results in excessively bleeding.• Pt with sever hemophilia presents withPt with sever hemophilia presents withrecurrent bleeding hemorrhage at followingrecurrent bleeding hemorrhage at followingsitessites• Joint most characteristics site is knee, elbow,Joint most characteristics site is knee, elbow,ankle, and hip.ankle, and hip.• Mucus membrane internal bleeding of mouth,Mucus membrane internal bleeding of mouth,lips, gums, brain and kidneylips, gums, brain and kidney• Muscle haematoma esp. calf and Psoas muscleMuscle haematoma esp. calf and Psoas muscle• RxRx• Factor VIII infusionFactor VIII infusion
HAEMOPHILLIA – B (CHRISTMASHAEMOPHILLIA – B (CHRISTMASDISEASE)DISEASE)• Due to diff: of factor IXDue to diff: of factor IX• S/Symptoms:S/Symptoms:• Same in type ASame in type A• RxRx• Factor IX infusionFactor IX infusion• Long Term ComplicationLong Term Complication• COMPLICATIONCOMPLICATION due to repeateddue to repeatedhemorrhage:hemorrhage:• Arthropathy of large joints eg knee, elbowArthropathy of large joints eg knee, elbow• Muscle atrophy due to haematomaMuscle atrophy due to haematoma• Mononeuropathy due to pressure ofMononeuropathy due to pressure ofhaematoma.haematoma.• COMPLICATION due to therapyCOMPLICATION due to therapy• Antifactor VIII antibody developsAntifactor VIII antibody develops• Virus transmission Hepatitis A-B-C-D + HIVVirus transmission Hepatitis A-B-C-D + HIV
DISSAMINATEDDISSAMINATEDINTRAVASCULARINTRAVASCULARCOAGULATIONCOAGULATION• DIC is condition characterized by thrombosisDIC is condition characterized by thrombosiswithin circulation. DIC can be induced bywithin circulation. DIC can be induced byvariety of diff: mechanism in no: of diverse butvariety of diff: mechanism in no: of diverse butdistinct clinical situations.distinct clinical situations.• Endothelial cell damage eg endotoxic in G –veEndothelial cell damage eg endotoxic in G –vesepticemia results in tissue factor release whichsepticemia results in tissue factor release whichin turn leads to coagulation cascade throughin turn leads to coagulation cascade throughextrinsic pathway.extrinsic pathway.• The presence thromboplastin from damagedThe presence thromboplastin from damagedtissue, placenta, fat embolus/following braintissue, placenta, fat embolus/following braininjury may activate coagulationinjury may activate coagulation• This result in consumption platelets andThis result in consumption platelets andcoagulation factors which secondarily activationcoagulation factors which secondarily activationof fibrinolysis leading to bleeding tendency.of fibrinolysis leading to bleeding tendency.
Causes Of DIC:Causes Of DIC:Infectious:Infectious:• E ColiE Coli• Nessieria meningitisNessieria meningitis• Strep pneumoniaStrep pneumonia• MalariaMalariaObstetricObstetric• RPOCRPOC• AbruptioplacentaeAbruptioplacentae• Amniotic fat embolismsAmniotic fat embolisms• Pre-eclampsiaPre-eclampsia
CancerCancer• LungLung• PancreasPancreas• ProstateProstateClinical Features:Clinical Features:• DIC leads to bleeding, thrombosis,DIC leads to bleeding, thrombosis,bleeding far from common thanbleeding far from common thanthrombosisthrombosis• Subacute DIC:Subacute DIC:• Occurs primarily in cancerous pts resultsOccurs primarily in cancerous pts resultsin superficial + deep venous thrombosisin superficial + deep venous thrombosis
Other Manifestation:Other Manifestation:• high incidence of cardio respiratoryhigh incidence of cardio respiratoryfailurefailureLAB:LAB:• ThrombocytopeniaThrombocytopenia• Prolong PTProlong PT• APPTT may be normal/increasedAPPTT may be normal/increased• Low fibrinogenLow fibrinogen• Increased level D-dimmerIncreased level D-dimmerRxRx• Underlying causeUnderlying cause
General Measures:General Measures:• Correction of dehydration, renal failure,Correction of dehydration, renal failure,acidosis and shockacidosis and shockReplacement:Replacement:• Platelets transfusion if platelets countsPlatelets transfusion if platelets countsbelow 10,000μg/lbelow 10,000μg/l• Fibrinogen with cryoprecipitate toFibrinogen with cryoprecipitate tomaintain plasma fibrinogen level abovemaintain plasma fibrinogen level above150 mg/dl150 mg/dl• FFPFFP• When thrombosis i-e DVT, PulmonaryWhen thrombosis i-e DVT, Pulmonarytheir give Heparin.their give Heparin.