3rd year pathology

1. Thrombocytopenia & VWD
Presentation by Dr Hassan Yar
Demonstrator GMC

2. Thrombocytopenia
• Characterized by abnormally low levels of platelets in the blood
• Most common coagulation disorder among ICU patients
• Seen in 20% of medical patients and a third of surgical patients
• Platelets < 150,000/ml ; Normal (150,000-450,000/ml)
• 2.5% of normal people < 150,000/ml
• Recent drop ≥ 50%, even if normal platelets count

3. Increased risk of bleeding
• if < 60,000 - with minor trauma
• if < 12,000 - spontaneous
• If < 6,000 - severe, life threatening
The bleeding is usually mucosal skin bleeding or petechiae.

4. Presentation
• usually has no symptoms and is picked up on a routine labs
• Symptoms:
1. epistaxis
2. gingival bleeding
3. meno/ metrorrhagia
4. tend to bleed immediately after minor trauma
5. cerebral bleeding
• Signs:
1. Ecchymoses
2. Petechiae
3. Purpura

6. Idiopathic thrombocytopenic purpura

7. Causes
Thrombocytopenia can be acquired or hereditary, but categorically
remember the following:
• Decreased platelet production
• Increased platelet destruction
• Drug induced
• Other

10. Decreased production
• Hypocellular BM
1. Infections(MMR, varicella, parvovirus, hepatitis C EBV, HIV, rickettsias)
2. Live attenuated vaccines
3. Drugs
4. Aplastic anemia
5. Alcohol
6. Autoantibody -against the thrombopoietin receptor (SLE)
• Hypercellular BM
1. Leukemias
2. MDS
3. Severe vit B12 /folate deficient anemia

11. • Marrow replacement
1. Myelofibrosis
2. Solid malignancies
3. Granulomas

12. Increased destruction
• Immune –mediated
1. Primary ITP
2. Secondary: infectious, CLL, Antiphospholipid syndrome, lymphoma
3. Allo-immunization (post-transfusion)
• Non-immune mediated
1. MAHA (TTP-HUS, DIC)
2. Evan Syndrome: thrombocytopenia + hemolytic anemia
3. Vascular prostheses/ bypass; trauma
4. Cavernous hemangioma
5. HELLP syndrome -in pregnant women

13. Drug Induced
These medications can induce thrombocytopenia through direct
myelosuppression:
• Valproic acid
• Methotrexate
• Carboplatin
• Interferon
• Isotretinoin
• Panobinostat
• H2 blockers and proton-pump inhibitors

14. Others
• Dilutional thrombocytopenia — massive blood transfusion with PRBC
(> 20 units of PRBCs /24H)
• Distributional thrombocytopenia caused by splenic sequestration:
1. Portal hypertension
2. Cirrhosis
3. Splenomegaly
4. Hypothermia
• Snake bite
• Niacin toxicity

15. Von Willebrand Disease
• Deficient function of von Willebrand Factor
1. Large glycoprotein
2. Synthesized by endothelial cells and megakaryocytes
3. Present in platelets
• Two key roles in hemostasis
1. Carrier of factor VIII (intrinsic coagulation pathway)
2. Binds platelets to endothelium and other platelets

16. • Most common inherited bleeding disorder
• Affects up to 1 percent of population
• Gene mutations causes ↓ level or function of vWF
• Most cases autosomal dominant (males=females)

17. Pathophysiology
• Defective primary hemostasis (intrinsic pathway)
1. Decreased adherence to vascular injury
2. Inadequate platelet plug formation prolongs bleeding time.

19. Presentation
• postoperative bleeding
• gingival bleeding
• Epistaxis
• Easy bruising
Location of oral bleeds was as follows:
1. labial frenum, 60%
2. tongue, 23%
3. buccal mucosa, 17%
4. gingiva and palate, 0.5%

20. • The prevalence of VWD is about one in 100 individuals.
• The prevalence of clinically significant cases is one per 10,000.
• There are three Types based on defect in vWF.
1. Type 1, Type 2 and type 3
2. Varying degrees of bleeding tendency, usually mild
3. Severe internal bleeding and bleeding into joints are uncommon in all but the most
severe type, VWD type 3.

22. Diagnosis
• CBC
• aPTT
• PT-INR
• Fibrinogen levels
• For Quantitative analysis: VWF antigen assay
• For Qualitative analysis: a collagen binding assay or a ristocetin
cofactor activity (RiCof)
• Factor VIII levels

23. Treatment
Treatment depends on the scenario of coagulopathy or bleeding;
• Desmopressin
• Recombinant vWF
• Blood Transfusion
• Oral contraceptives for meno-metrorrhagia
• Factor VIII concentrates for pre-op patients