This document discusses various bleeding disorders including: - Definition as a disorder characterized by spontaneous or excessive bleeding following trauma. - Etiologies including vessel wall abnormalities (congenital or acquired like vasculitis) and platelet functional disorders. - Specific disorders discussed in more detail include von Willebrand disease, hemophilia, Bernard-Soulier syndrome, and Glanzmann's thrombasthenia. - Clinical features, laboratory findings, and treatment approaches are provided for many of the disorders.

1. BLEEDINGBLEEDING
DISORDERDISORDER
Prof. Rafi Ahmed GhoriProf. Rafi Ahmed Ghori
FCPSFCPS
LIAQUAT UNIVERSITY OFLIAQUAT UNIVERSITY OF
MEDICAL & HEALTH SCIENCESMEDICAL & HEALTH SCIENCES
JAMSHOROJAMSHORO

2. 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 be
congenital OR acquired i-e vasculitiscongenital OR acquired i-e vasculitis
may result in purpuric lesions.may result in purpuric lesions.

3. CAUSES OFCAUSES 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

4. HERIDITARY HEOMORRAGICHERIDITARY HEOMORRAGIC
TELANGECTSIASIS:TELANGECTSIASIS:
• Dominant inherited condition. There is aDominant inherited condition. There is a
telengectiasis and small aneurysms found ontelengectiasis and small aneurysms found on
finger tips, face, nasal passages, tongue andfinger tips, face, nasal passages, tongue and
GIT.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 from
bleeding (epistaxis).bleeding (epistaxis).
• Estrogens may be tried.Estrogens may be tried.

5. EHLERS DANLOS DISEASE:EHLERS DANLOS DISEASE:
• Congenital disorder of collagen synthesisCongenital disorder of collagen synthesis
in which capillaries are poorly supportedin which capillaries are poorly supported
by s/c collagen and ecchymosis areby s/c collagen and ecchymosis are
commonly observed.commonly observed.

6. B.PLATELETS FUNCTIONALB.PLATELETS FUNCTIONAL
DISORDER:DISORDER:
• Thrombocytopenia (quantitative plateletsThrombocytopenia (quantitative platelets
dysfunction)dysfunction)
• S/S:S/S:
– Dominated clinically by petechialDominated clinically by petechial
cutaneous bleeding, intracranialcutaneous bleeding, intracranial
bleeding and arising from mucusbleeding and arising from mucus
membrane/surface.membrane/surface.
• Characterized by decreased plateletsCharacterized by decreased platelets
count and prolong bleeding timecount and prolong bleeding time

7. 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 afterExcessive platelets consumption after
their release into circulation i-e ITP, DICtheir release into circulation i-e ITP, DIC
etc.etc.
• Platelets sequestration in enlargedPlatelets sequestration in enlarged
spleen i-e HYPERSPLEENISMspleen i-e HYPERSPLEENISM

8. Causes:Causes:
Marrow DisorderMarrow Disorder
• Aplastic anemiaAplastic anemia
• Hematologic malignancyHematologic malignancy
• Myelodysplastic disorderMyelodysplastic disorder
• B12 deff.B12 deff.
• Chronic alcoholismChronic alcoholism

9. Non Marrow DisorderNon Marrow Disorder
Immune disordersImmune disorders
• ITPITP
• Drug inducedDrug induced
• Sec: CLL, SLESec: CLL, SLE
• Post transfusionPost transfusion

10. DICDIC
TTPTTP
• HU syndrome HyperspleenismHU syndrome Hyperspleenism
• SepsisSepsis
• HeamangiomasHeamangiomas
• Viral infectionViral infection
• Liver failure.Liver failure.

11. IDIOPATHIC THROMBOTICIDIOPATHIC THROMBOTIC
THROMBOCYTOPENICTHROMBOCYTOPENIC
PURPURA.PURPURA.
• Autoimmune antibody IgG is formed againstAutoimmune antibody IgG is formed against
unknown 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, where
spleenic macrophages with Fc bind to antibodyspleenic macrophages with Fc bind to antibody
coated platelets.coated platelets.

12. Clinical Features:Clinical Features:
In Children:In Children:
• Commonly occur in children, often precipitatedCommonly occur in children, often precipitated
by 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.

13. • 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-e
platelets below 10,000 /ml.platelets below 10,000 /ml.
• Bone marrow will appear normal.Bone marrow will appear normal.

14. RxRx
• PREDENISONONE:PREDENISONONE: 1-2 mg/kg/day.1-2 mg/kg/day.
• SPLEEN ECTOMY: immunoglobulin 1g/kg/daySPLEEN ECTOMY: immunoglobulin 1g/kg/day
2-3 days.2-3 days.
• DANAZOLE:DANAZOLE:600mg/day response rate is600mg/day response rate is
50%50%
• IMMUNOSUPPERESSIVE DRUGS: i-eIMMUNOSUPPERESSIVE DRUGS: i-e
vincristine, 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 is
initially controlled with prednisolone,initially controlled with prednisolone,
spleenectomy is definite Rx.spleenectomy is definite Rx.

15. • EVANS SYNDROME:EVANS SYNDROME:
• ITP + Autoimmune hemolytic anemia 10%ITP + Autoimmune hemolytic anemia 10%
cases.cases.
• These pts shows spherocytosis, reticulocytosisThese pts shows spherocytosis, reticulocytosis
+ anemia.+ anemia.

16. TIP:TIP:
THROMBOTICTHROMBOTIC
THROMBOCYTOPENIC PURPURA:THROMBOCYTOPENIC PURPURA:
Def:Def:
• TIP is an uncommon syndrome withTIP is an uncommon syndrome with
microangiopathic 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, renal
abnormalities are less commonly seen.abnormalities are less commonly seen.
• Pathogenesis may be diff: of von Willibrand’sPathogenesis may be diff: of von Willibrand’s
disease factors clearing protease, in some casedisease factors clearing protease, in some case
antibody directed against protease.antibody directed against protease.

17. Clinical features:Clinical features:
• Primarily in young aged 20-25 yr, slightlyPrimarily in young aged 20-25 yr, slightly
common in female.common in female.
• Pts present with anemia, bleeding, feverPts present with anemia, bleeding, fever
and neurological manifestation.and neurological manifestation.
• Neurological symptoms may be, headNeurological symptoms may be, head
ache, confusion aphasia, alteration inache, confusion aphasia, alteration in
consciousness from lethargy to comeconsciousness from lethargy to come
with more advanced one may see hemiwith more advanced one may see hemi
paresis + seizures.paresis + seizures.

18. LAB:LAB:
• Anemia, reticulocytosis and occasionalAnemia, reticulocytosis and occasional
circulating nucleated cells.circulating nucleated cells.
• Hallmark microangiopathic picture withHallmark microangiopathic picture with
fragmented RBC’s i-e (schistocytes, helmetfragmented 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 increasedHemolysis may be manifested with increased
indirect bilirubin, hemoglobinemia, methemindirect bilirubin, hemoglobinemia, methem
albuminia which impart a brown colour toalbuminia which impart a brown colour to
plasma.plasma.
• LDH markedly increased.LDH markedly increased.
• Coomb’s test –ve.Coomb’s test –ve.
• Coagulation test: PT, APPTT, fibrinogenCoagulation test: PT, APPTT, fibrinogen
Normal, (fibrin degradation product) FDP mayNormal, (fibrin degradation product) FDP may
be elevatedbe elevated..

19. • Rx:Rx:
• Plasmapheresis with /without prednisone antiPlasmapheresis with /without prednisone anti
platelets aspirin 325 mg/daily , dipyridamole 75platelets aspirin 325 mg/daily , dipyridamole 75
mg × TDS may be given.mg × TDS may be given.
• Combination spleenectomy, steroids andCombination spleenectomy, steroids and
dextran 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 plasma
pharesis while 20% pts will be chronic andpharesis while 20% pts will be chronic and
relapsing.relapsing.

20. B.QUALITATIVE PLETELETB.QUALITATIVE PLETELET
DISORDERDISORDER::
CONGENITAL:CONGENITAL:
• Glansmann’s thrombostheniaGlansmann’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 diseaseAcquired storage pool disease
• Fibrin degradation productsFibrin degradation products
• Von Willibrand’s diseaseVon Willibrand’s disease

21. BERNARD SOULIER SYNDROME:BERNARD SOULIER SYNDROME:
• Bare Autosomal recessive intrinsic plateletsBare 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 whichreceptor for von Willibrand’s factor which
mediates platelets adhesions to submediates platelets adhesions to sub
endothelium.endothelium.
• Clinical Features:Clinical Features:
• Presents with mucosal bleeding and postPresents with mucosal bleeding and post
operatively as well.operatively as well.
• LAB:LAB:
• Thrombocytopenia may be present, andThrombocytopenia may be present, and
abnormally large.abnormally large.
• BT is prolongedBT is prolonged
• Von Willibrand’s factor NormalVon Willibrand’s factor Normal
• Rx:Rx:

22. GLANSMANN’sGLANSMANN’s
THROMBASTHENIA:THROMBASTHENIA:
• Rae Autosomal recessive disorder.Rae Autosomal recessive disorder.
• Platelets unable to aggregate b/c lack ofPlatelets 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 plateletsfor 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 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 typical
against (ADP, collagen, thrombin) butagainst (ADP, collagen, thrombin) but
aggregate in respond to risocetin by separateaggregate in respond to risocetin by separate
mechanismmechanism
• RxRx::
• Platelet transfusionPlatelet transfusion

23. VON-WILLIBRAND’SVON-WILLIBRAND’S
DISEASE:DISEASE:
• It’s a transmitted by Autosomal dominant andIt’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 andVWF is synthesized by endothelial cells and
megakaryocytic that performs two functionsmegakaryocytic that performs two functions
– It acts as carrier protein for factor VIII whichIt acts as carrier protein for factor VIII which
it is non-covalently bound. A deff: thereforeit is non-covalently bound. A deff: therefore
leads 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 sub
endothelium eg collagen allowing platelets toendothelium eg collagen allowing platelets to
adhere to damaged vessel walls. There foreadhere to damaged vessel walls. There fore
decreased diff: of VWF leads to prolongdecreased diff: of VWF leads to prolong
bleeding after minor trauma.bleeding after minor trauma.

24. • 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 lien
accomplished by sec: reduction in factor VIIIaccomplished 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 VWFDesmopressin 0.3 μg/kg, after which VWF
levels usually raise 3 in 30-90 minuteslevels usually raise 3 in 30-90 minutes
• MASSIVE HAEMORRHAGES:MASSIVE HAEMORRHAGES:
• Factor VIIIFactor VIII

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

26. CONGENITAL BLEEDINGCONGENITAL BLEEDING
DISORDER:DISORDER:
• HAEMOPHILIAHAEMOPHILIA
• It is hereditary disease affecting malesIt is hereditary disease affecting males
but transmitted by females andbut transmitted by females and
characterized by prolong coagulation andcharacterized by prolong coagulation and
life long tendency to excessivelife long tendency to excessive
hemorrhagehemorrhage
• HEAMOPHILIA – A CLASSIC TRUEHEAMOPHILIA – A CLASSIC TRUE
HAEMOPHILIAHAEMOPHILIA
• X-linked disorderX-linked disorder
• Due deff: of factor VIIIDue deff: of factor VIII

27. • C/F:C/F:
• Although it is congenital disorder bleedingAlthough it is congenital disorder bleeding
occurs as bruising when babies are about 6occurs 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 withPt with sever hemophilia presents with
recurrent bleeding hemorrhage at followingrecurrent bleeding hemorrhage at following
sitessites
• 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

28. HAEMOPHILLIA – B (CHRISTMASHAEMOPHILLIA – B (CHRISTMAS
DISEASE)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 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 ofMononeuropathy 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 + HIVVirus transmission Hepatitis A-B-C-D + HIV

29. ACQUIRED BLEEDINGACQUIRED BLEEDING
DISORDER:DISORDER:
• DICDIC
• LIVER DISEASELIVER DISEASE
• RENAL DISEASERENAL DISEASE

30. DISSAMINATEDDISSAMINATED
INTRAVASCULARINTRAVASCULAR
COAGULATIONCOAGULATION
• DIC is condition characterized by thrombosisDIC is condition characterized by thrombosis
within circulation. DIC can be induced bywithin circulation. DIC can be induced by
variety of diff: mechanism in no: of diverse butvariety of diff: mechanism in no: of diverse but
distinct clinical situations.distinct clinical situations.
• Endothelial cell damage eg endotoxic in G –veEndothelial cell damage eg endotoxic in G –ve
septicemia results in tissue factor release whichsepticemia results in tissue factor release which
in turn leads to coagulation cascade throughin turn leads to coagulation cascade through
extrinsic pathway.extrinsic pathway.
• The presence thromboplastin from damagedThe presence thromboplastin from damaged
tissue, placenta, fat embolus/following braintissue, placenta, fat embolus/following brain
injury may activate coagulationinjury may activate coagulation
• This result in consumption platelets andThis result in consumption platelets and
coagulation factors which secondarily activationcoagulation factors which secondarily activation
of fibrinolysis leading to bleeding tendency.of fibrinolysis leading to bleeding tendency.

31. 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

32. CancerCancer
• LungLung
• PancreasPancreas
• ProstateProstate
Clinical Features:Clinical Features:
• DIC leads to bleeding, thrombosis,DIC leads to bleeding, thrombosis,
bleeding far from common thanbleeding far from common than
thrombosisthrombosis
• Subacute DIC:Subacute DIC:
• Occurs primarily in cancerous pts resultsOccurs primarily in cancerous pts results
in superficial + deep venous thrombosisin superficial + deep venous thrombosis

33. Other Manifestation:Other Manifestation:
• high incidence of cardio respiratoryhigh 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

34. General Measures:General Measures:
• Correction of dehydration, renal failure,Correction of dehydration, renal failure,
acidosis and shockacidosis and shock
Replacement:Replacement:
• Platelets transfusion if platelets countsPlatelets transfusion if platelets counts
below 10,000μg/lbelow 10,000μg/l
• Fibrinogen with cryoprecipitate toFibrinogen with cryoprecipitate to
maintain plasma fibrinogen level abovemaintain plasma fibrinogen level above
150 mg/dl150 mg/dl
• FFPFFP
• When thrombosis i-e DVT, PulmonaryWhen thrombosis i-e DVT, Pulmonary
their give Heparin.their give Heparin.

35. THANKTHANK
YOUYOU