The document discusses various hemorrhagic and thrombotic disorders. It describes the normal hemostasis process and key tests used in evaluation. Several specific disorders are then covered in more detail, including immune thrombocytopenic purpura (ITP), hemophilia, von Willebrand disease, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), antiphospholipid syndrome (APS), and various thrombotic disorders. For each condition, it discusses causes, clinical presentation, diagnosis and management.

1. Hemorrhagic & thrombotic diorders

2. Hemostasis
 Four step process
 1- primary hemostatic plug-
interaction between
damaged endothelium &
platelets
 2- coagulation
 3- stabilization of fibrin
network
 4- fibrinolysis, restoring
patency of vessel
 Tests
 Platelet count, bleeding time
 aPTT, PT/INR
 Thrombin time-TT
 FDP/D-dimer

3. Disorders of hemostasis
 ITP- immune thrombocytopenic purpura
 Hemophilia
 von Willebrand disease
 TTP/HUS
 DIC- disseminated intravascular coagulation
 Anti-phospholipid syndrome
 Thrombotic disorders

4. ITP
 Immune destruction of platelets
 Idiopathic, r/o secondary causes
 Usually chronic in adults, with durable
remission in ~1/3rd
 Low platelet count causes-
 Petechiae, purpura
 Bleeding- oral cavity, menorrhagia, GIT, CNS

5. Treatment
 Steroids
 Anti-D in Rh +ve patients
 Steroid sparing- Mycophenolate, Azathioprine
 Thrombopoietin receptor antagonist-
Romiplostim-SC, Eltrombopag- oral
 Splenectomy
 Platelet transfusion with IVIG & steroids-
in emergency

6. Hemophilia
 Hereditary, X-linked recessive
 More in males, females are carriers
 Causes bleeding due to clotting factor
deficiency- VIII-A, IX-B, XI-C-AD
 Complications- hemarthrosis, CNS bleed &
transfusion related infections
 Severity-
 Mild- 5-40% normal level of active clotting factor
 Moderate- 1-5%
 Severe- <1%

7. Management
 Dx-
 Bleeding tendency
 Prolonged aPTT, with normal PT & platelet count
 Factor VIII/IX levels
 Rx- prophylactic or on demand
 Recombinant factor VIII
 Cryoprecipitate
 Refractory- porcine factor VIII, recombinant factor VII
 Avoid NSAIDs, trauma, contact physical sports
 Exercise to strengthen muscles & protect joints

8. von Willebrand disease
 Most common hereditary coagulation abnormality-
prevalence ~1 in 100-
 Type I & II- AD
 Type III- AR- most severe form
 Due to deficiency of vWF,
required for platelet adhesion
 Causes superficial bleeding tendency,
severe internal or joint bleeding is rare
 aPTT prolonged, with normal PT & platelet count
 Rx- OCP in females, Desmopressin, cryoprecipitate,
Humate-P (factor VIII concentrate rich in vWF)

9. Thrombotic Thrombocytopenic Purpura
 Rare
 Most due to inhibition of enzyme ADAMTS13,
responsible for cleaving large multimers of
vWF into small units
 Causes extensive microscopic thrombosis,
with platelet consumption
 Microthromboses cause end- organ
dysfunction
 Hemolysis is due to shear stress,
producing schistocytes

10. Cause
 Idiopathic- autoimmune,
severely decreased ADAMTS13 activity
 Secondary- associated with
 Cancer
 BMT
 Pregnancy
 HIV-1 infection
 Drugs- Quinine, Clopidogrel, cyclosporine, Tacrolimus,
Mitomycin-C, Interferon
 Hereditary- Upshaw-Schulman syndrome

11. Management
 Clinical presentation-
 Fever
 Thrombocytopenia- petechiae, purpura
 MAHA- anemia, jaundice, schistocytes
 Fluctuating neurologic symptoms
 Acute renal insufficiency
 Dx- clinical, thrombocytopenia,
normal PT/aPTT
 Rx-
 Plasmapheresis, with supportive treatment
 Refractory- steroids, Cyclophosphamide,
Rituximab, splenectomy

12. Disseminated Intravascular Coagulation
 Also called consumptive coagulopathy
 Due to pathological activation of coagulation
cascade, leading to widespread clotting &
resultant bleeding
 Causes-
 Sepsis, complicated malaria
 Cancer- APL, lung/pancreas/prostate/stomach
 Abruptio placentae, eclampsia, amniotic fluid embolism
 Massive trauma, burns, snake bite, heat stroke

13. Management
 s/s- mostly acutely ill patient, bleeding from
multiple sites, with RI & gangrene
 Dx-
 Thrombocytopenia
 Prolonged PT & aPTT
 Low fibrinogen
 Raised FDP
 Rx- reversal of underlying cause
 Support with FFP, anticoagulants, platelet transfusion
 Px- overall ~1/3rd
die, sepsis>trauma

14. APLS
 Autoimmune disease
 Causes-
 Arterial-CVA or venous thrombosis-DVT
 Pregnancy related complications like abortion, still-
birth, preterm delivery, pre-eclampsia
 Primary or secondary
 Dx-
 Clinical presentation- vascular thrombosis or pregnancy event
 +ve aPL Abs- lupus anticoagulant & anticardiolipin Abs
 Rx- aspirin, heparin, warfarin-INR 2-3

15. Thrombosis
 Coagulation is counter-balanced &
regulated by-
 Antithrombin-III
 Protein C & S- inactivate factor V & VIII
 Tissue factor pathway inhibitor
 Fibrinolytic system

16. Thrombotic disorders
 AT-III deficiency-
 Autosomal dominant, also lost in urine in NS
 Increased thrombosis- DVT/PE, mesenteric vein
 Dx- low functional level of AT-III
 Rx- large dose heparinlifelong Warfarin
 Protein C deficiency-
 Warfarin induced skin necrosis is characteristic
 Rx- heparin, followed by Warfarin
 Protein S deficiency- physiologically in
pregnancy & in patients on OCP
 Defective fibrinolysis/ PAI inhibitors