This document discusses various bleeding disorders including definitions, etiologies, and clinical features. It covers vessel wall abnormalities like hereditary hemorrhagic telangiectasia and Ehlers Danlos disease. Platelet disorders discussed include quantitative issues like thrombocytopenia and qualitative issues such as Bernard Soulier syndrome. Coagulation disorders covered include hemophilia A, hemophilia B, and acquired disorders like disseminated intravascular coagulation and liver disease. Specific conditions like idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, and von Willebrand disease are explained in detail.

1. BLEEDINGBLEEDING
DISORDERSDISORDERS
DR.RAFI AHMED GHORI
Professor
Medical Unit I
LUMHS Jamshoro.

2. BLEEDING DISORDERBLEEDING DISORDER
Definition:Definition:
Disorder characterized by
Spontaneous bleeding.
Excessive bleeding
following trauma.

3. EtiologyEtiology
VESSEL WALL ABNORMALITIES:
PLATELETS DISORDER:
COAGULATION DISORDER:

4. VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:
Vessel wall abnormalities may be congenital OR acquired i-e
vasculitis may result in purpuric lesions.
CAUSES OF NON-THROMBOCYTOPENIC PURPURA:
 1. Senile purpura
 2. Fictitious purpura
 3. Henoch-Schonlein purpura
 4. Vasculitis
 5. Paraprotienaemias
 6. Purpura fulminans
 7. Embolic purpura

5. VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:
HERIDITARY HEMORRHAGIC
TELANGECTSIASIS:
 Dominant inherited condition. There is a telengectiasis and
small aneurysms found on finger tips, face, nasal passages,
tongue and GIT.
 Small group of people develop pulmonary A/V
malformation.
 Pt either develops recurrent bleeding/epistaxis/iron deff:
anemia due to occult GIT bleeding.
Rx.Rx.
 Iron therapy for blood loss.
 .Local cautery/laser therapy for single lesion from bleeding
(epistaxis).
 Estrogens may be tried.

6. VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:
EHLERS DANLOS DISEASE:
Congenital disorder of collagen
synthesis in which capillaries are poorly
supported by s/c collagen and
ecchymosis are commonly observed.

7. PLATELETS DISORDER:PLATELETS DISORDER:
QUANTITATIVE PLATELETS
DYSFUNCTION
QUALITATIVE PLETELET
DISORDER:

8. PLATELETS DISORDER:PLATELETS DISORDER:
QUANTITATIVE PLATELETSQUANTITATIVE PLATELETS
DYSFUNCTIONDYSFUNCTION ((Thrombocytopenia) Thrombocytopenia)
Mechanism:
 1 Failure of megakaryocytic maturation.
 2 Excessive platelets consumption after their release into
circulation i-e ITP, DIC etc.
 3 Platelets sequestration in enlarged spleen i-e
HYPERSPLEENISM.
S/S:
• Petechial cutaneous bleeding, intracranial bleeding and
oozing from mucus membrane/surface.
• Characterized by decreased platelets count and prolong
bleeding time.

9. ((Thrombocytopenia)Thrombocytopenia) Causes:Causes:
Marrow Disorder
 Aplastic anemia
 Hematologic
malignancy
 Myelodysplastic
disorder
 B12 deff.
 Chronic alcoholism
Non Marrow Disorder
Immune disorders
ITP
Drug induced
Sec: CLL, SLE
Post transfusion
DIC
TTP
HU syndrome
Hyperspleenism
Sepsis
Heamangiomas
Viral infection
Management:
• Rx Underlying cause
• Platelet transfusion

10. IDIOPATHIC THROMBOCYTOPENICIDIOPATHIC THROMBOCYTOPENIC
PURPURA.PURPURA.
Autoimmune antibody IgG is formed against
unknown antigen of platelets membrane/surface.
Antipletelet antibody binds to complement, platelets
are not destroyed by direct lysis.
Rather destruction takes place in spleen, where
spleenic macrophages with Fc bind to antibody
coated platelets.

11. IDIOPATHIC THROMBOCYTOPENICIDIOPATHIC THROMBOCYTOPENIC
PURPURA.PURPURA. (Clinical Features)(Clinical Features)
In Children:
Often precipitated by viral infection and usually
self limited
 Asymptomatic not febrile.
 Present with mucosal/skin bleeding,
mennorrhagia, purpura, petechiae.
Adults:
• Commonly affects female.
• Ratio 2:1 (male/female ratio)
• Peak incidence 20-50 years of age.

12. IDIOPATHIC THROMBOCYTOPENICIDIOPATHIC THROMBOCYTOPENIC
PURPURA.PURPURA.
Δ LAB:
 platelets below 10,000 /ml.
 Bone marrow will appear normal.
Rx
 PREDENISONONE: 1-2 mg/kg/day.
 SPLEENECTOMY: immunoglobulin 1g/kg/day 2-3 days.
 DANAZOLE: 600mg/day response rate is 50%
 IMMUNOSUPPERESSIVE DRUGS: i-e vincristine,
vinblastine, azathioprine, cyclosprin, cyclophosphomide.
Prognosis:
 The prognosis for remission is good. Disease is initially
controlled with prednisolone, spleenectomy is definite Rx.

13. EVANS SYNDROME:EVANS SYNDROME:
ITP + Autoimmune hemolytic anemia
10% cases.
These pts shows spherocytosis,
reticulocytosis + anemia.

14. THROMBOTIC THROMBOCYTOPENICTHROMBOTIC THROMBOCYTOPENIC
PURPURA:TTP:PURPURA:TTP:
TIP is an uncommon syndrome with
Microangiopathic hemolytic anemia,
Thrombocytopenia and
Markedly increased LDH,
Non-infectious fever,
Neurologic disorder,
Renal abnormalities are less commonly seen.
Pathogenesis may be diff: of von Willibrand’s disease
factors clearing protease, in some case antibody
directed against protease.

15. TTP:TTP:
Clinical features:
20-25 yr
Slightly common in female.
Anemia
Bleeding
Fever
Neurological symptoms
Head ache
Confusion aphasia
Altered consciousness
Hemi paresis + seizures.

16. TTP:TTP:
LAB:
Blood CP
Anemia
Reticulocytosis
Circulating nucleated cells.
Microangiopathic picture
Fragmented RBC’s i-e
(schistocytes, helmet
cells, triangle forms)
Thrombocytopenia.
Hemolysis, Increased
Indirect bilirubin
Hemoglobinemia
Methem-albuminia.
Increased LDH.
Coomb’s test –ve.
Coagulation test:
Normal PT, APPTT,
fibrinogen.
Elevated. FDP(fibrin
degradation product)
may be

17. TTP:TTP:
Rx:
Plasmapheresis with /without prednisone, anti
platelets aspirin 325 mg/daily , dipyridamole 75
mg × TDS may be given.
Combination spleenectomy, steroids and dextran
may be used with success.
Immuno suppressive therapy i-e
(cyclophosphomide).
Prognosis:
80-90 % Pts recover completely with plasma
pharesis while 20% pts will be chronic and
relapsing.

18. QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER
CONGENITAL:
Glansmann’s
thrombosthenia
Bernard souliar
syndrome
Storage pool disease
•ACQUIRED
•Myeloproliferative disorder.
•Uremia
•Drugs i-e NSAIDS Aspirin
•Autoantibody
•Paraprotiens
•Acquired storage pool disease
•Fibrin degradation products
•Von Willibrand’s disease

19. QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER
BERNARD SOULIER SYNDROME:BERNARD SOULIER SYNDROME:
 Autosomal recessive intrinsic platelets disorder.
 lack of glycoprotein (41 b) receptor for von Willibrand’s
factor.
Clinical Features:
 Presents with mucosal bleeding and post operatively as
well.
LAB:
 Thrombocytopenia may be present, and abnormally large.
 BT is prolonged
 Von Willibrand’s factor Normal
Rx:
 Platelet transfusion

20. QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER
GLANSMANN’s THROMBASTHENIA:GLANSMANN’s THROMBASTHENIA:
 Autosomal recessive disorder.
 Lack of receptors (containing glycoprotein II b + III a) for
fibrinogen on platelets.
Clinical Features:
 Mucosal bleeding
LAB:
 Platelets no’s and morphology are normal
 B.T is prolonged
 Platelets fails to aggregate in respond to typical agent (ADP,
collagen, thrombin) but aggregate in respond to risocetin.
Rx:
 Platelet transfusion

21. QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER
VON-WILLIBRAND’S DISEASE:VON-WILLIBRAND’S DISEASE:
Autosomal dominant and gene for (VWF) is
located on chromosome 12.
VWF is synthesized by endothelial cells and
megakaryocytic
It acts as carrier protein for factor VIII which it is
non-covalently bound. A defect therefore leads to
decreased plasma factor VIII level.
It forms bridges b/w platelets and sub endothelium
eg collagen allowing platelets to adhere to damaged
vessel walls. There fore defect of VWF leads to
prolong bleeding after minor trauma.

22. QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER
VON-WILLIBRAND’S DISEASE:VON-WILLIBRAND’S DISEASE:
Clinical Features:
 Mucosal bleeding as already discussed.
LAB:
 Reduced level of VWF which often accomplished by sec:
reduction in factor VIII and prolonged bleeding time
(B.T)
Rx:
 MILD HAEMORRHAGES:
Desmopressin 0.3 μg/kg, after which VWF levels usually
raise 3 in 30-90 minutes
 MASSIVE HAEMORRHAGES:

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

24. HEAMOPHILIA – A (CLASSIC TRUE
HAEMOPHILIA)
HAEMOPHILLIA – B (CHRISTMAS
DISEASE)
COAGULATION DISORDER:COAGULATION DISORDER:
CONGENITAL BLEEDINGCONGENITAL BLEEDING
DISORDER:DISORDER:

25. HEAMOPHILIA – A (CLASSIC TRUEHEAMOPHILIA – A (CLASSIC TRUE
HAEMOPHILIA)HAEMOPHILIA)
 X-linked disorder
 Due to defect of factor VIII
C/F:
 Bleeding occurs as bruising when babies are about 6 month
old.Trauma results in excessively bleeding.
 Recurrent bleeding hemorrhage at following sites
knee, elbow, ankle, and hip.
 Mucus membrane internal bleeding of mouth, lips, gums,
brain and kidney
 Muscle haematoma esp. calf and Psoas muscle
Rx
 Factor VIII infusion

26. HAEMOPHILLIA – B (CHRISTMASHAEMOPHILLIA – B (CHRISTMAS
DISEASE)DISEASE)
 Due to deff: of factor IX
S/S:
 Same in type A
Rx
 Factor IX infusion
LONG TERM COMPLICATION
COMPLICATION due to repeated hemorrhage:
 Arthropathy of large joints eg knee, elbow
 Muscle atrophy due to haematoma
 Mononeuropathy due to pressure of haematoma.
COMPLICATION due to therapy
 Antifactor VIII antibody develops
 Virus transmission Hepatitis A-B-C-D + HIV

27. COAGULATION DISORDERCOAGULATION DISORDER
ACQUIRED BLEEDINGACQUIRED BLEEDING
DISORDERDISORDER
DIC
LIVER DISEASE
RENAL DISEASE

28. DISSAMINATED INTRAVASCULARDISSAMINATED INTRAVASCULAR
COAGULATIONCOAGULATION
 DIC is condition characterized by thrombosis within
circulation. DIC can be induced by variety of different
mechanism.
 Endothelial cell damage eg endotoxic in G –ve septicemia
results in tissue factor release which in turn leads to
coagulation cascade through extrinsic pathway.
 The presence thromboplastin from damaged tissue,
placenta, fat embolus/following brain injury may activate
coagulation
 This results in consumption of platelets and coagulation
factors which secondarily activation of fibrinolysis leading
to bleeding tendency.

29. DICDIC::
CAUSES
Infectious:
 E Coli
 Nessieria meningitis
 Strep pneumonia
 Malaria
Obstetric
 RPOC
 Abruptio placentae
 Amniotic fat embolisms
 Pre-eclampsia
Cancer
 Lung
 Pancreas
 Prostate
CLINICAL FEATURES:
Bleeding, thrombosis, bleeding
far from common than
thrombosis.
Subacute DIC:
Occurs primarily in cancerous
pts results in superficial + deep
venous thrombosis.
Other Manifestation:
High incidence of cardio
respiratory failure

30. DICDIC
LAB:
Thrombocytopenia
Prolong PT
APPTT may be
normal/increased
Low fibrinogen
Increased level D-dimmer

31. Treatment of DICTreatment of DIC
Rx Underlying cause.
General Measures:
 Correction of dehydration
 Renal failure
 Acidosis and
 Shock
Replacement:
 Platelets transfusion if platelets counts below 10,000μg/l
 Fibrinogen with cryoprecipitate to maintain plasma
fibrinogen level above 150 mg/dl
 FFP
 When thrombosis i-e DVT, Pulmonary their give Heparin.

32. THANKYOU