Bleeding or Hemostasis

Question 1

What is Virkhoff’s Triad?

Answer 1

1. Venous stasis (post-MI, stroke, or post-operation) - inhibited removal of coagulation factors
2. Hypercoaguability state - multi-factorial and multiplicative or additive: Genetic (Factor V Leiden (5% of pop.), immobolization, age, surgery, trauma, neoplasms, hormone related, heart failure, blood dycrasias
3. Endothelial Damage - exposes endothelium to prompt hemostasis - less inhibition of coagulation and decreased fibrinolysis

Question 2

What are the physical exam features of primary hemostatic bleeding disorders?

And what are causes of those bleeding disorders?

Answer 2

Physical Exam

bleeding from mucocutaneous tissues, bleeding from superficial areas –> petechia, epitaxis, purpura, mucous membranes, excessive periods

Causes

• thrombocytopenia
• VWD
• platelet function disorders (drug acquired causes)
• vascular abnormalities

Question 3

What are the common laboratory tests for primary hemostatic bleeding disorders?

Answer 3

1. Platelet aggregation studies - if func. of plt in Q
2. Closure time - if func. of plt in Q
3. CBC and smear
4. VWF studies

Question 4

What are the clinical features of the secondary hemostatic disorders?

Answer 4

1. hematomas
2. muscle bleeding
3. hemathrosis
4. bleeding is delayed and prolonged, common after surgery

Question 5

Laboratory Tests for Secondary hemostatic diseases?

Answer 5

• aPTT (activated partial thromboplastin time)
  
  • Measures the intrinsic pathway
    
    • Factors 8,9,10,11,12
• PT (prothrombin time or INR - developed to monitor warfarin)
  
  • ​Factor VII

Can have elevated PTT and PT if common pathway (X —V—-> II)

Question 6

What are the three mechanisms that produce thrombocytopenia?

Answer 6

1. Increased destruction - autoimmune or not?
2. Descresed production - look at the bone marrow
3. Sequesteration - look at splenomegaly

Question 7

List the platelet production problems

Answer 7

• Descreased megakaryopoesis
  
  • Leukemias or displacement via cancer, aplastic anemias, toxic suppression (chemotherapy)
• Ineffective
• • nutritional megaloblastic anemia - vitamin b12 or folate
    
    • Folate inhibitor
    • Congentital

Question 8

List the platelet destruction problems

Answer 8

• Immune
  
  • allo - post transfusion
  • auto - ITP, usually with SLE or CLL
• Drug induced HIT (heparin induced…)
• Non-immune
  
  • Sepsis, DIC, TTP, HUS, HHELP

Question 9

List differences between acute and chronic ITP

Answer 9

• Chronic
  
  • Adults, severe bleeding risk when platelets < 30, which indicates treatment of immuno suppression (corticosteroids first line, IVIG also can work, anti-Rho, splenoctomy is second line)
• Acute
  
  • Kids
  • 80% will resolve without treatment
  • serious bleeding is rare
  • Post-viral

Question 10

Describe HIT

Answer 10

Heparin induced thrombocytopenia

• Drug reaction, less common with LMWH
• administer protamine to counteract heparin and change drugs immediately
• thrombosis
• skin necrosis at site of injection
• 50% fall in plts

Question 11

What is the most common causes of acquired platelet function disorder?

Answer 11

COX-1 inhibitor (ASA)

• stops the releases of thromboxane A2
• Also, there are systemic illnesses and hematological manifestations that causes function disorders*

Question 12

List three congentital platelet disorders (rare or common?)

Answer 12

• Glanzzman’s Thromboesthemia
• Bernard Soulier Syndrome
• Gray Platelet Syndrome

Question 13

What does vitamin K do?

Answer 13

Allows the carboxylation of factors II, VII, IX, and X, which allows these clotting factors to bind the phospholipids on the surface of platelets

Question 14

List the causes of vitamin K deficiency

Answer 14

1. Diet
2. Malabsorption (Celiac’s, IBD)
   
   1. And disorders of fat malabsorption (pancreatic or bile disorders)
3. Too much Vitamin A and E
4. Antibiotics – impaired normal flora
5. Drugs – warfarin

Question 15

What causes hemorrhagic disease of the newborn?

Answer 15

Insufficient vitamin K

Question 16

Describe how liver disease can result in coagulopathy

Answer 16

• Most of the clotting factors are produced in the liver
  
  • Exceptions are VIII (endothelial cells) and VWF (endothelial cells or megakaryocytes)
• Acute liver disease will have a prolonged PT
  
  • VII has the shortest half-life and is the first to be affected
• Chronic liver disease will have prolonged PT/PTT

Question 17

What is the purpose of INR?

Answer 17

INR was developed to make dose-adjustments for warfarin in order descrease the likelihood of bleeding or thrombotic events

Standardized PT

Question 18

What is the DDX for elevated PTT/normal PT?

Answer 18

• X-linked deficiencies
  
  • Hemophilia A (VIII)
  • Hemophilia B (IX)
• Autosomal Recessive
  
  • Factor XI
• Autosomal Dominant
  
  • VWF
• Antiphospholipid antibodies
• Heparin
• Factor VIII inhibitor

Question 19

Describe the pathophysiology of antiphospholipid antibodies

Answer 19

Lupus type inhibitor is the most common one

• Inhibit the phospholipid (high PTT), but does not interupt the physiological clotting cascade
• In fact, it actually leads to thrombosis
• Other complications include miscarriages
• Do a mixing study to rule-out

Question 20

VWF functions?

Answer 20

1. Binds platelet - platelet
2. Platelet - endothelium
3. binds VIII (part of fibrin clot formation!)

Question 21

VWD

1. 3 types

Answer 21

Type 1 - deficiency, equal low VWF antigen and activity

• Low or normal VIII

Type 2 - lower activity of VWF (function, many subtypes)

• low or normal VIII

Type 3 - extremely low antigen and activity, full deficiency

• < 10% of VIII

Question 22

Treatment of VWD

Answer 22

• DDAVP (desmopression)
  
  • Stimulates release of VWF from subendothelial cells
  • Works well for type 1 (unless severe), some type 2, but not type 3
• VWF/VIII replacement therapy
  
  • Needed in type 3, severe type 1
  • IV virally inactivated
  • Indicated post or pre-operatively or other indication of bleeding
• anti-fibrolytics
  
  • adjuct
  • Used alone only in mild symptomatic VWF disease
  • contra-indicated with hematuria

Question 23

Polycythemia Vera

Answer 23

• stem cell disorder
• elevated RBC mass +/- increase WBC and platelets
• symptoms due to high red cells
• bleeding and thrombotic ecvents
• erythomelalgia - burning in hands, feet and erythema
• pruitus
• gout, plethora on face, palms
• splenomegaly and hepatosplenomegaly is common
• LOOK for hemoglobin over 165 (W) or 185 (M) and JAK2 mutation. Plus minor criteria (bone marrow biopsy with hypercellularikty, low EPO levels, endogenous erythroid colony formation in vitro)

Treatment

• phelbotomy to keep hemtocrit < 45%
• ASA to prevent thrombosis
• hydroxyurea (if refractory to phlebotomy)
• allopurionol and antihistamines for symptoms

Complications

• Bleeding or thrombosis, progression to AML
• median surival is 10-20 yrs

Question 24

List the Well’s Score criteria

Answer 24

1. Stasis (>3 day in hospital)
2. Prior Surgery (< 6 months)
3. Active Cancer
4. Prior DVT
5. Calf swelling (>3cm)
6. Leg swelling
7. Pitting edema
8. Collateral superficial veins
9. localized tenderness

2 or MORE = DVT likely

Question 25

Simplified Well’s score for PE

Answer 25

1. Symptoms of DVT = 3
2. No other Dx = 3
3. Immobilization = 1.5
4. Malignancy = 1
5. Hemoptysis = 1
6. Prior DVT = 1.5
7. Tachycardic (>100) = 1.5

PE suspected if 4 or >

Question 26

What are the 2 primary options for imaging a VTE?

Answer 26

1. CT pulmonary angiography - visualizes the blood vessels
2. Compression ultrasonography

Also available

1. Ventilation and perfusion (V/P) when CTPA is contraindicated (preg., renal insufficiency, reaction to contrast medium)

Question 27

How can you tell a PE is really bad?

Answer 27

1. Right ventricular strain
2. elevated BNP and troponin

Question 28

List the common/serious side effects of heparin, as well as its mechanism of action and monitoring

Answer 28

• Heparin is monitored with aPTT (1.5 - 2.5 is ideal)I
• heparin is often started at hospital in VTE cases
  
  • Risk of bleeding, especially with prior surgery
  • Major risk is heparin induced thrombocytopenia (HIT), which results in more clotting! Platelets are being used up, hence the penia
    
    • argatroban is an anti-thrombin which is indicated during HIT
• Heparin is an indirect anti-thrombin activator, it helps X and IX come together with anti-thrombin
• LMWH is a better alternative, can be taken orally, preferred in cancer and pregancy, no need for monitoring, lower risk of HIT and bleeding

Question 29

Outline the basic plan behind seeing a VTE patient as well as describe warfarin’s mechanism of action

Answer 29

• Do the Well’s score, D-dimer if unlikely
• CT or compression ultrasonography

ACUTE

• heparin, oral Xa inhibitors (rivaroxaban), LMWH (preg. or active cancer)
• Monitor the aPTT
• If extremely serious, may need to use fibrinolytics
• IVC shunt not really used, only in cases where fibrinolytics are contraindicated (high risk of bleeding)

CHRONIC

• Warfarin (need to overlap with heparin for first 5 days because of initital hypercoagulable state from decreased protein C)
  
  • inhibits II, VII, IX, and X via inhibiting vitamin K glycosylation of these factors
  • INR monitoring required
• LMWH
• Oral Xa inhibitors
• Direct thrombin inhibitors
  
  • dabigitran

Question 30

What is Hydroxurea used for?

Answer 30

1. Sickle cell disease (increases Fetal hemoglobin, helpful during acute chest syndrome)
2. Myeloproliferative syndromes, especially ET and PV
3. Formally used in CML, now replaced by GLEEVEC
4. HIV/AIDS