BLEEDING BLEEDING DISORDERDISORDER

Prof. Rafi Ahmed GhoriProf. Rafi Ahmed GhoriFCPS FCPS

LIAQUAT UNIVERSITY OF LIAQUAT UNIVERSITY OF MEDICAL & HEALTH SCIENCES MEDICAL & HEALTH SCIENCES

JAMSHOROJAMSHORO

BLEEDING DISORDERBLEEDING DISORDER

• Definition:Definition:

• Disorder characterized by Disorder characterized by spontaneous/ excessive bleeding spontaneous/ excessive bleeding following trauma.following trauma.

• Etiology:Etiology:

• A.VESSEL WALL ABNORMALITIES:A.VESSEL WALL ABNORMALITIES:

• Vessel wall abnormalities may be Vessel wall abnormalities may be congenital OR acquired i-e vasculitis congenital OR acquired i-e vasculitis may result in purpuric lesions.may result in purpuric lesions.

CAUSES OF CAUSES OF NON-NON-THROMBOCYTOPENICTHROMBOCYTOPENIC PURPURA:PURPURA:

• Senile purpuraSenile purpura

• Fictitious purpuraFictitious purpura

• Henoch-Schonlein purpuraHenoch-Schonlein purpura

• VasculitisVasculitis

• ParaprotienaemiasParaprotienaemias

• Purpura fulminansPurpura fulminans

• Embolic purpuraEmbolic purpura

HERIDITARY HEOMORRAGIC HERIDITARY HEOMORRAGIC TELANGECTSIASIS:TELANGECTSIASIS:• Dominant inherited condition. There is a Dominant inherited condition. There is a

telengectiasis and small aneurysms found telengectiasis and small aneurysms found on finger tips, face, nasal passages, on finger tips, face, nasal passages, tongue and GIT.tongue and GIT.

• Small group of people develop pulmonary Small group of people develop pulmonary A/V : anemia due to occult GIT bleeding.A/V : anemia due to occult GIT bleeding.

• Rx.Rx.• Iron therapy for blood loss.Iron therapy for blood loss.• Local cautery/laser therapy for single Local cautery/laser therapy for single

lesion from bleeding (epistaxis).lesion from bleeding (epistaxis).• Estrogens may be tried.Estrogens may be tried.

EHLERS DANLOS DISEASE:EHLERS DANLOS DISEASE:

• Congenital disorder of collagen Congenital disorder of collagen synthesis in which capillaries are synthesis in which capillaries are poorly supported by s/c collagen and poorly supported by s/c collagen and ecchymosis are commonly observed.ecchymosis are commonly observed.

B.PLATELETS FUNCTIONAL B.PLATELETS FUNCTIONAL DISORDER:DISORDER:

• Thrombocytopenia (quantitative Thrombocytopenia (quantitative platelets dysfunction)platelets dysfunction)

• S/S:S/S:– Dominated clinically by petechial Dominated clinically by petechial

cutaneous bleeding, intracranial cutaneous bleeding, intracranial bleeding and arising from mucus bleeding and arising from mucus membrane/surface.membrane/surface.

• Characterized by decreased platelets Characterized by decreased platelets count and prolong bleeding timecount and prolong bleeding time

Management:Management:• Underlying causeUnderlying cause• Platelet transfusionPlatelet transfusion

Mechanism of Thrombocytopenia:Mechanism of Thrombocytopenia:• Failure of megakaryocytic maturation.Failure of megakaryocytic maturation.• Excessive platelets consumption after Excessive platelets consumption after

their release into circulation i-e ITP, their release into circulation i-e ITP, DIC etc.DIC etc.

• Platelets sequestration in enlarged Platelets sequestration in enlarged spleen i-e HYPERSPLEENISMspleen i-e HYPERSPLEENISM

Causes:Causes:

Marrow DisorderMarrow Disorder

• Aplastic anemiaAplastic anemia

• Hematologic malignancyHematologic malignancy

• Myelodysplastic disorderMyelodysplastic disorder

• B12 deff.B12 deff.

• Chronic alcoholismChronic alcoholism

Non Marrow DisorderNon Marrow Disorder

Immune disordersImmune disorders

• ITPITP

• Drug inducedDrug induced

• Sec: CLL, SLESec: CLL, SLE

• Post transfusionPost transfusion

DICDICTTPTTP

• HU syndrome HyperspleenismHU syndrome Hyperspleenism

• SepsisSepsis

• HeamangiomasHeamangiomas

• Viral infectionViral infection

• Liver failure.Liver failure.

IDIOPATHIC THROMBOTIC IDIOPATHIC THROMBOTIC THROMBOCYTOPENIC THROMBOCYTOPENIC

PURPURA.PURPURA.

• Autoimmune antibody IgG is formed Autoimmune antibody IgG is formed against unknown antigen of platelets against unknown antigen of platelets membrane/surface.membrane/surface.

• Antipletelet antibody binds to Antipletelet antibody binds to complement, platelets are not destroyed complement, platelets are not destroyed by direct lysis.by direct lysis.

• Rather destruction takes place in spleen, Rather destruction takes place in spleen, where spleenic macrophages with Fc bind where spleenic macrophages with Fc bind to antibody coated platelets.to antibody coated platelets.

Clinical Features:Clinical Features:

In Children:In Children:• Commonly occur in children, often Commonly occur in children, often

precipitated by viral infection and usually precipitated by viral infection and usually self limitedself 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-e Hallmark of disease is thrombocytopenia i-e

platelets 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/day SPLEEN ECTOMY: immunoglobulin 1g/kg/day

2-3 days.2-3 days.

• DANAZOLE:DANAZOLE:600mg/day response rate is 600mg/day response rate is 50%50%

• IMMUNOSUPPERESSIVE DRUGS: i-e IMMUNOSUPPERESSIVE DRUGS: i-e vincristine, vinblastine, azathioprine, vincristine, vinblastine, azathioprine, cyclosprin, cyclophosphomide.cyclosprin, cyclophosphomide.

• Prognosis:Prognosis:• The prognosis for remission is good. The prognosis for remission is good.

Disease is initially controlled with Disease is initially controlled with prednisolone, spleenectomy is definite Rx.prednisolone, spleenectomy is definite Rx.

• EVANS SYNDROME:EVANS SYNDROME:• ITP + Autoimmune hemolytic anemia 10% ITP + Autoimmune hemolytic anemia 10%

cases.cases.

• These pts shows spherocytosis, These pts shows spherocytosis, reticulocytosis + anemia.reticulocytosis + anemia.

TIP: TIP: THROMBOTIC THROMBOTIC

THROMBOCYTOPENIC PURPURA:THROMBOCYTOPENIC PURPURA: Def: Def: • TIP is an uncommon syndrome with TIP is an uncommon syndrome with

microangiopathic hemolytic anemia, microangiopathic hemolytic anemia, thrombocytopenia and markedly increased thrombocytopenia and markedly increased LDH, Non-infectious fever, Neurologic LDH, Non-infectious fever, Neurologic disorder, renal abnormalities are less disorder, renal abnormalities are less commonly seen.commonly seen.

• Pathogenesis may be diff: of von Willibrand’s Pathogenesis may be diff: of von Willibrand’s disease factors clearing protease, in some disease factors clearing protease, in some case antibody directed against protease.case antibody directed against protease.

Clinical features:Clinical features:

• Primarily in young aged 20-25 yr, Primarily in young aged 20-25 yr, slightly common in female.slightly common in female.

• Pts present with anemia, bleeding, Pts present with anemia, bleeding, fever and neurological manifestation.fever and neurological manifestation.

• Neurological symptoms may be, head Neurological symptoms may be, head ache, confusion aphasia, alteration in ache, confusion aphasia, alteration in consciousness from lethargy to come consciousness from lethargy to come with more advanced one may see with more advanced one may see hemi paresis + seizures.hemi paresis + seizures.

LAB:LAB:• Anemia, reticulocytosis and occasional Anemia, reticulocytosis and occasional

circulating nucleated cells. circulating nucleated cells. • Hallmark microangiopathic picture with Hallmark microangiopathic picture with

fragmented RBC’s i-e (schistocytes, helmet fragmented RBC’s i-e (schistocytes, helmet cells, triangle forms) on smear.cells, triangle forms) on smear.

• Thrombocytopenia invariably present.Thrombocytopenia invariably present.• Hemolysis may be manifested with Hemolysis may be manifested with

increased indirect bilirubin, increased indirect bilirubin, hemoglobinemia, methem albuminia which hemoglobinemia, methem albuminia which impart a brown colour to plasma.impart a brown colour to plasma.

• LDH markedly increased.LDH markedly increased.• Coomb’s test –ve.Coomb’s test –ve.• Coagulation test: PT, APPTT, fibrinogen Coagulation test: PT, APPTT, fibrinogen

Normal, (fibrin degradation product) FDP Normal, (fibrin degradation product) FDP may be elevatedmay be elevated..

• Rx:Rx:• Plasmapheresis with /without prednisone Plasmapheresis with /without prednisone

anti platelets aspirin 325 mg/daily , anti platelets aspirin 325 mg/daily , dipyridamole 75 mg × TDS may be given.dipyridamole 75 mg × TDS may be given.

• Combination spleenectomy, steroids and Combination spleenectomy, steroids and dextran may be used with success.dextran may be used with success.

• Immuno suppressive therapy i-e Immuno suppressive therapy i-e (cyclophosphomide(cyclophosphomide).).

• Prognosis:Prognosis:• 80-90 % Pts recover completely with plasma 80-90 % Pts recover completely with plasma

pharesis while 20% pts will be chronic and pharesis while 20% pts will be chronic and relapsing.relapsing.

B.QUALITATIVE PLETELET B.QUALITATIVE PLETELET DISORDERDISORDER::CONGENITAL:CONGENITAL:

• Glansmann’s thrombosthenia Glansmann’s thrombosthenia • Bernard souliar syndromeBernard souliar syndrome• Storage pool diseaseStorage pool disease

ACQUIREDACQUIRED • Myeloproliferative disorder.Myeloproliferative disorder.• UremiaUremia• Drugs i-e NSAIDS AspirinDrugs i-e NSAIDS Aspirin• AutoantibodyAutoantibody• ParaprotiensParaprotiens• Acquired storage pool disease Acquired 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 platelets Bare Autosomal recessive intrinsic platelets disorder.disorder.

• Occurs due to lack of glycoprotein (41 b) Occurs due to lack of glycoprotein (41 b) receptor for von Willibrand’s factor which receptor for von Willibrand’s factor which mediates platelets adhesions to sub mediates platelets adhesions to sub endothelium.endothelium.

• Clinical Features:Clinical Features:• Presents with mucosal bleeding and post Presents with mucosal bleeding and post

operatively as well.operatively as well.• LAB:LAB:• Thrombocytopenia may be present, and Thrombocytopenia may be present, and

abnormally large.abnormally large.• BT is prolonged BT is prolonged • Von Willibrand’s factor Normal Von Willibrand’s factor Normal • Rx:Rx:• Platelet transfusionPlatelet transfusion

GLANSMANN’s GLANSMANN’s THROMBASTHENIA:THROMBASTHENIA:

• Rae Autosomal recessive disorder.Rae Autosomal recessive disorder.• Platelets unable to aggregate b/c lack of Platelets unable to aggregate b/c lack of

receptors (containing glycoprotein II b + III a) receptors (containing glycoprotein II b + III a) for fibrinogen which bridges b/w the platelets for fibrinogen which bridges b/w the platelets during aggregation.during aggregation.

• Clinical Features:Clinical Features:• Mucosal bleedingMucosal bleeding• LAB:LAB:• Platelets no’s and morphology are normal Platelets no’s and morphology are normal • B.T is prolonged B.T is prolonged • Platelets fails to aggregate in respond to Platelets fails to aggregate in respond to

typical against (ADP, collagen, thrombin) but typical against (ADP, collagen, thrombin) but aggregate in respond to risocetin by aggregate in respond to risocetin by separate mechanism separate mechanism

• RxRx::• Platelet transfusionPlatelet transfusion

VON-WILLIBRAND’S VON-WILLIBRAND’S DISEASE:DISEASE:

• It’s a transmitted by Autosomal dominant and It’s a transmitted by Autosomal dominant and gene for (VWF) is located on chromosome 12gene for (VWF) is located on chromosome 12

• VWF is synthesized by endothelial cells and VWF is synthesized by endothelial cells and megakaryocytic that performs two functions megakaryocytic that performs two functions – It acts as carrier protein for factor VIII It acts as carrier protein for factor VIII

which it is non-covalently bound. A deff: which it is non-covalently bound. A deff: therefore leads to decreased plasma factor therefore leads to decreased plasma factor VIII level.VIII level.

– It form bridges b/w platelets and sub It form bridges b/w platelets and sub endothelium eg collagen allowing platelets endothelium eg collagen allowing platelets to adhere to damaged vessel walls. There to adhere to damaged vessel walls. There fore decreased diff: of VWF leads to prolong fore decreased diff: of VWF leads to prolong bleeding 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 lien Reduced level of VWF which of lien

accomplished by sec: reduction in factor VIII accomplished by sec: reduction in factor VIII and prolonged bleeding time (B.T)and prolonged bleeding time (B.T)

• Rx:Rx:• MILD HAEMORRHAGES:MILD HAEMORRHAGES:

• Desmopressin 0.3 μg/kg, after which VWF Desmopressin 0.3 μg/kg, after which VWF levels usually raise 3 in 30-90 minutes levels usually raise 3 in 30-90 minutes

• MASSIVE HAEMORRHAGES:MASSIVE HAEMORRHAGES:

• Factor VIII Factor VIII

C. COAGULATION DISORDER:C. COAGULATION DISORDER:

• Coagulation factor disorder can either can Coagulation factor disorder can either can either arise from single factor usually either arise from single factor usually “congenital deficiency” eg factor VIII “congenital deficiency” eg factor VIII resulting in HAEMOPHILCIA-A or multiple resulting in HAEMOPHILCIA-A or multiple factor which is acquired eg Sec: to liver factor which is acquired eg Sec: to liver disease or warfarin therapy. disease or warfarin therapy.

CONGENITAL BLEEDING CONGENITAL BLEEDING DISORDER:DISORDER:

• HAEMOPHILIAHAEMOPHILIA • It is hereditary disease affecting males It is hereditary disease affecting males

but transmitted by females and but transmitted by females and characterized by prolong coagulation characterized by prolong coagulation and life long tendency to excessive and life long tendency to excessive hemorrhage hemorrhage

• HEAMOPHILIA – A CLASSIC TRUE HEAMOPHILIA – A CLASSIC TRUE HAEMOPHILIAHAEMOPHILIA

• X-linked disorder X-linked disorder • Due deff: of factor VIIIDue deff: of factor VIII

• C/F:C/F:• Although it is congenital disorder bleeding Although it is congenital disorder bleeding

occurs as bruising when babies are about 6 occurs as bruising when babies are about 6 month 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 with Pt with sever hemophilia presents with recurrent bleeding hemorrhage at following recurrent bleeding hemorrhage at following sites sites

• Joint most characteristics site is knee, Joint most characteristics site is knee, elbow, ankle, and hip.elbow, ankle, and hip.

• Mucus membrane internal bleeding of Mucus membrane internal bleeding of mouth, lips, gums, brain and kidneymouth, lips, gums, brain and kidney

• Muscle haematoma esp. calf and Psoas Muscle haematoma esp. calf and Psoas muscle muscle

• RxRx• Factor VIII infusion Factor VIII infusion

HAEMOPHILLIA – B (CHRISTMAS HAEMOPHILLIA – B (CHRISTMAS DISEASE)DISEASE)

• Due to diff: of factor IX Due 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• COMPLICATION COMPLICATION due to repeated due to repeated

hemorrhage: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 of Mononeuropathy due to pressure of

haematoma.haematoma.• COMPLICATION due to therapyCOMPLICATION due to therapy• Antifactor VIII antibody developsAntifactor VIII antibody develops• Virus transmission Hepatitis A-B-C-D + Virus transmission Hepatitis A-B-C-D +

HIVHIV

ACQUIRED BLEEDING ACQUIRED BLEEDING DISORDER:DISORDER:

• DICDIC

• LIVER DISEASE LIVER DISEASE

• RENAL DISEASERENAL DISEASE

DISSAMINATED DISSAMINATED INTRAVASCULAR INTRAVASCULAR COAGULATIONCOAGULATION

• DIC is condition characterized by DIC is condition characterized by thrombosis within circulation. DIC can be thrombosis within circulation. DIC can be induced by variety of diff: mechanism in no: induced by variety of diff: mechanism in no: of diverse but distinct clinical situations.of diverse but distinct clinical situations.

• Endothelial cell damage eg endotoxic in G –Endothelial cell damage eg endotoxic in G –ve septicemia results in tissue factor ve septicemia results in tissue factor release which in turn leads to coagulation release which in turn leads to coagulation cascade through extrinsic pathway.cascade through extrinsic pathway.

• The presence thromboplastin from damaged The presence thromboplastin from damaged tissue, placenta, fat embolus/following tissue, placenta, fat embolus/following brain injury may activate coagulationbrain injury may activate coagulation

• This result in consumption platelets and This result in consumption platelets and coagulation factors which secondarily coagulation factors which secondarily activation of fibrinolysis leading to bleeding activation of fibrinolysis leading to bleeding tendency.tendency.

Causes Of DIC: Causes Of DIC:

Infectious:Infectious:• E ColiE Coli

• Nessieria meningitisNessieria meningitis

• Strep pneumoniaStrep pneumonia

• MalariaMalaria

ObstetricObstetric• RPOCRPOC

• AbruptioplacentaeAbruptioplacentae

• Amniotic fat embolismsAmniotic fat embolisms

• Pre-eclampsiaPre-eclampsia

CancerCancer • LungLung• PancreasPancreas• ProstateProstate

Clinical Features:Clinical Features:• DIC leads to bleeding, thrombosis, DIC leads to bleeding, thrombosis,

bleeding far from common than bleeding far from common than thrombosisthrombosis

• Subacute DIC:Subacute DIC:• Occurs primarily in cancerous pts Occurs primarily in cancerous pts

results in superficial + deep venous results in superficial + deep venous thrombosisthrombosis

Other Manifestation:Other Manifestation:• high incidence of cardio respiratory high incidence of cardio respiratory

failurefailure

LAB:LAB:• ThrombocytopeniaThrombocytopenia• Prolong PTProlong PT• APPTT may be normal/increasedAPPTT may be normal/increased• Low fibrinogenLow fibrinogen• Increased level D-dimmerIncreased level D-dimmer

RxRx• Underlying causeUnderlying cause

General Measures:General Measures:

• Correction of dehydration, renal Correction of dehydration, renal failure, acidosis and shockfailure, acidosis and shock

Replacement:Replacement:

• Platelets transfusion if platelets Platelets transfusion if platelets counts below 10,000μg/lcounts below 10,000μg/l

• Fibrinogen with cryoprecipitate to Fibrinogen with cryoprecipitate to maintain plasma fibrinogen level maintain plasma fibrinogen level above 150 mg/dl above 150 mg/dl

• FFPFFP

• When thrombosis i-e DVT, Pulmonary When thrombosis i-e DVT, Pulmonary their give Heparin.their give Heparin.

THANK THANK YOUYOU