Pathology lecture for undergraduates

1. HEMORRHAGIC
DISORDERS
PART 2

2. Hemorrhagic disorders
Decreased platelet count/ function
• Idiopathic thrombocytopenic purpura (ITP)
• Thrombotic thrombocytopenic purpura(TTP)
• Hemolytic uremic syndrome
• DIC
• Dengue H. Fever
• Glanzman’s thromboasthenia
• Bernard Soulier syndrome

3. Thrombocytopenia
• Platelets’ ↓ed synthesis(B12/Folate def.,
leukemia, MDS, Sepsis, Dengue
H.Fever, HIV, Drugs CT, Valproic
acid etc.)
• ↓ed platelet survival (ITP, TTP,HUS,DIC,
DHF)
• Sequestration in spleen-
hypersplenism
• Dilutional  massive transfusion

4. Thrombotic thrombocytopenic
purpura (TTP)
• Rare disorder
• Micro-thrombi in small blood vessels.
• RBCs are trapped in microthrombi/shearing
effecthemolytic anemia (microangiopathic
anemia).
• Spontaneous aggragation of platelets
activation of coagulation cascade
consumption of platelets
(thrombocytopenia).

5. TTP- pathogenesis
• Idiopathic & secondary TTP.
IDIOPATHIC TTP
• Inhibition of the enzyme  ADAMTS13 by
antibodies/Inhibitors.
• ADAMTS13 is a metalloproteinase
breakdown of large circulating multimers of
vonWillebrand Factor into smaller units.
• If large vWF multimers persists tendency
for ↑ed platelet aggregation-thrombi

7. Secondary TTP
May be secondary to :
• Cancer
• Pregnancy
• Medication use (immuno-suppressants,
platelet aggregation inhibitors).
• BM transplantation.
• ADAMTS13 enzyme activity is not as
depressed as in idiopathic TTP
• Endothelial damage may be the cause.

8. Diagnosis of TTP
• Microangiopathic hemolytic anemia
• blood film  mechanical fragmentation of
red blood cells schistocytes.
• Jaundice
• Thrombocytopenia
• Neurological deficits.(microthrombi in CNS)
• Kidney failure.(microthrombi in kidney)

9. Fragmented RBCs- Schistocytes

10. schistocytes & helmet cells

11. Treatment of TTP
• Plasmapheresis  this is an exchange
transfusion  removal of patients’ plasma
(antiADAMTS13antibodies)through apheresis
: replacement with a donor fresh frozen
plasma or cryosupernatant.
• Duration : may range from 1-8 weeks.
• If pheresis is not availableFFPDanger of
volume overload.
• Mortality 95% for untreated patient

12. Hemolytic uremic syndrome
• Childhood HUS
• Adult HUS
• MICROANGIOPATHIC Hemolytic anemia,
acute renal failure(uremia),
thrombocytopenia.
• Thrombotic microangiopathy
• Coagulation factors are not
consumedcoagulation screen normal.

13. Childhood HUS-pathogenesis
• Most cases are preceded by an episode of
diarrhea caused by E.coli O157:H7 that
express Shiga like toxin (shiga producing
E.coli-SPEC) or EHEC.
• HUS follows an influenza like illness or
diarrhea with
bleedingsymptoms(hemetamesis or malena
or hematuria).
• In some children : neurological deficit may be
seen.

14. Childhood HUS-pathogenesis
• SPEC Toxin in blood attaches to
endothelium especially glomerular
endothelium inactivates ADAMTS13 
large multimers of vWF forms platelet
activationmicrothrombi in kidney and
throughout body.
• Thrombocytopenia bleeding
manifestations.

15. MICROANGIOPATHIC Hemolytic
anemia

16. Microthrombus in kidney

17. Microthrombi in kidney in HUS

18. Adult HUS
• HIV
• SLE, SCLERODERMA
• Post partum renal failure
• Malignant hypertension
• Antiphospholipid syndrome
• CT
• Immuno-suppressants.

19. Dengue Fever & DHF
• Febrile illness caused by 4 closely related virus
serotypes of genus flavivirus.
• Aedes aegypti or rarely Aedes albopictus
mosquitowhich feed during the daytime.
• Symptoms : sudden onset of severe headache,
myalgia and arthralgia.(Breakbone Fever)
• Petechial dengue rash usually first appear on lower
limbs and then on chest - then body.

20. Aedes aegypti

21. Dengue rash

22. Rashes & subconjunctival bleeding

23. Bleeding manifestations in DF &
DHF
• Nausea vomiting & diarrhea.
• Hemetamesis & malena
• Spontaneous bruising, mucosal & gum
bleeding
• Encephalitic manifestations

24. Diagnosis of DF & DHF
• Thrombocytopenia (< 1Lac/cumm) & relative
leucopenia.
• Positive tourniquet test.
• Hemoconcentration (↑ed PCV  >20%)
due to extensive plasma leakage in
extravascular space.
• Denge serology : IgM & IgG Antibodies. Both
IgG and IgM are produced after 5–7 days
• PCR – viral nucleic acid

25. Treatment
• Oral and or IV fluid  for good hydration
• Platelet transfusion : if count falls
below20,000cumm.
• In case of excessive bleeding : whole blood
transfusion.
• Aspirin & NSAIDS should be avoided.
• Paracetamol can be given.

26. DIC
• Pathological activation of coagulation
• Small thrombi forms in blood vessels through
out the body.
• Consumption of coagulation factors and also
platelets. (consumptive coagulopathy).
• Abnormal bleeding e.g from injection sites,
GI Bleeding, hemoptysis or bleeding from
surgical wounds etc.

27. Pathogenesis
• Complication of pregnancy.(Tissue factor
release)
• Cancer (TF release)
• Septicemia (gram –ve /
staphylococcal)endotoxin
(lipopolysaccharide) / toxic shock syndrome
toxin-1 release widespread endothelial
injury & activation of coagulation cascade
DIC
• Normal blood supply to organs
disruptedmulti- organ failure.

28. Diagnosis
• Peripheral blood  schistocytes
• Thrombocytopenia
• Prolonged PT & APTT
• Low Fibrinogen level
• Increased levels of fibrin degradation
products like D-dimers.