BLEEDING AND THROMBOTIC DISORDERS

Question 1

What’s your diagnosis?

Child

Abrupt onset of petechiae/ecchymoses around 1-2 weeks after viral illness

BT-Prolonged

Platelet count- low

PT- normal

PTT- normal

The bone marrow aspirate shows an increase in immature megakaryocytes

Deborah Dalmeida MD

Answer 1

Acute immune thrombocytopenic purpura (ITP)

Deborah Dalmeida MD

Question 2

Vitamin K dependent coagulation factors

Deborah Dalmeida MD

Answer 2

II, VII, IX and X

Deborah Dalmeida MD

Question 3

1. Inherited thrombotic disorder caused by replacement of arginine by glutamine at position 506.
2. Which coagulation factor levels are increased in this disorder as a result of the single base change?

Deborah Dalmeida MD

Answer 3

1. Factor V Leiden
2. Factor Va

Deborah Dalmeida MD

Question 4

List the causes for DIC

Deborah Dalmeida MD

Answer 4

STOP Making Thrombi

• Sepsis (gram negative)
• Trauma
• Obstetric complications
• Pancreatitis
• Malignancy
• Transfusion

Deborah Dalmeida MD

Question 5

List some antiphospholipid antibodies

Deborah Dalmeida MD

Answer 5

anticardiolipin antibodies

anti-β2-glycoprotein antibodies

lupus anticoagulants

Deborah Dalmeida MD

Question 6

1. Does heparin prolong PT or PTT ?
2. How?

Deborah Dalmeida MD

Answer 6

1. Prolongation of PT and PTT

Gotcha ;)

2. Heparin activates ATIII- this in turn inhibits both sides of the coagulation cascade – VIIa, IXa, Xa, XIa and thrombin

Deborah Dalmeida MD

Question 7

A 56 year old female with atrial fibrillation is started on a drug. 2 days later , she develops a lesion on her left lower limb as seen below. PT is prolonged.

1. What is the reason for the development of the lesion?

2. If this woman had an inherited Protein C deficiency, would she have a greater risk of developing this lesion?

Deborah Dalmeida MD

Answer 7

1. Warfarin induced skin necrosis
2. Protein C together with Factor VII has the shortest half life (6 and 14 hours respectively). In normal individuals, the fall in protein C activity following the start of warfarin is generally not of clinical significance, but in heterozygotes with levels of protein C that are about half of normal, a further drop in protein C activity during the first day of therapy can trigger thrombosis in the skin.

Deborah Dalmeida MD

Question 8

Following platelet activation, Glycoprotein IIb/IIIa located on the surface of a platelet is able to cross link with another platelet via binding to which substance?

Deborah Dalmeida MD

Answer 8

Fibrinogen

Deborah Dalmeida MD

Question 9

dyspnea, acute renal failure

BT-prolonged

Platelet count- Low

PT- Prolonged

PTT-Prolonged

Fibrinogen- decreased1.

1.Diagnosis?

2. Most sensitive screen?

Deborah Dalmeida MD

Answer 9

1. DIC
2. Elevated D-Dimers

Deborah Dalmeida MD

Question 10

1. Diagnosis?

Neurologic symptoms
Fever
Kidney Failure

BT-Prolonged

Platelet count- Low

PT- Normal

PTT- Normal

2. Etiology?

Deborah Dalmeida MD

Answer 10

1. Thrombotic Thrombocytopenic Purpura (TTP)
2. Deficiency of ADAMTS13

Deborah Dalmeida MD

Question 11

How does heparin cause life threatening thrombosis?

Deborah Dalmeida MD

Answer 11

1. large complexes of IgG, PF4, and heparin detach from platelets, , attach to endothelial cells, and damage the endothelial cells, causing activation of the coagulation system
2. Enhances AT III’s affinity for thrombin, IXa,Xa, XIa and XIIa

Deborah Dalmeida MD

Question 12

glomerular capillaries occluded by microthrombi

renal failure

Schistocytes on a peripheral smear

BT- Prolonged

Platelet count- Low

PT- Normal

PTT- Normal

history of bloody diarrhea after eating an undercooked hamburger at a restaurant

Deborah Dalmeida MD

Answer 12

HUS

Deborah Dalmeida MD

Question 13

2 properties of antiphospholipid antibodies

Deborah Dalmeida MD

Answer 13

a. Bind to phospholipid surface
b. bind to the phospholipid part of the PTT reagent

Deborah Dalmeida MD

Question 14

Bernard Soulier/ vW disease?

BT- Prolonged

Platelet count-Low

PT- Normal

PTT- Normal

reduced ristocetin cofactor activity which does not normalize after the addition of normal plasma

Deborah Dalmeida MD

Answer 14

Bernard-Soulier syndrome

Deborah Dalmeida MD

Question 15

superficial bleeding localized to skin and mucous membranes

Deborah Dalmeida MD

Answer 15

Purpura

Deborah Dalmeida MD

Question 16

3 examples of malignancy associated with thromboses

Deborah Dalmeida MD

Answer 16

Trousseau Syndrome i.e migratory superficial thrombophlebitis

Thrombosis with chronic DIC

Nonbacterial thrombotic (marantic) endocarditis

Deborah Dalmeida MD

Question 17

Mechanism of heparin induced thrombocytopenia

Deborah Dalmeida MD

Answer 17

Drug + PF 4 = antigenic complex which reacts with antibodies–> immune complex–> bind to platelet Fc receptor –>platelet activation

Deborah Dalmeida MD

Question 18

1. One test that you will perform to distinguish decreased production from increased destruction of a coagulation factor
2. Explain the steps and interpretation of mixing studies.

Deborah Dalmeida MD

Answer 18

1. Mixing studies

2.

Procedure: Normal plasma mixed with patient plasma

Interpretation:

a. Correction of the PT and/or PTT indicates decreased production of coagulation factors.
b. No correction of the PT and/or the PTT indicates immune destruction of coagulation factors is present. Antibody is also destroying the coagulation factor in the normal plasma that is added to the test tube.

Deborah Dalmeida MD

Question 19

easy bruising

recurrent joint bleeds

BT- Normal

Platelet count- Normal

PT- Normal

PTT- Prolonged

What are the chances of a female heterozygous carrier with a normal male partner, conceiving an affected son?

Deborah Dalmeida MD

Answer 19

50%

The diseases is Hemophilia A , X-linked recessive

Deborah Dalmeida MD

Question 20

Defect assoc with Bernard Soulier?

Deborah Dalmeida MD

Answer 20

inherited deficiency of the platelet membrane glyco­protein complex Ib-IX.

Deborah Dalmeida MD

Question 21

Consequence of a single base substitution in the 3′ untranslated region of the prothrombin gene

Deborah Dalmeida MD

Answer 21

30% higher plasma levels of structurally normal prothrombin

Deborah Dalmeida MD

Question 22

Young female

malar rash, renal failure

PS- Thrombocytopenia

PTT – Prolonged

Mixing study – does not correct the PTT

Kidney biopsy- Glomeruli show multiple capillary and arterial thromboses

Diagnosis?

Deborah Dalmeida MD

Answer 22

ANTIPHOSPHOLIPID ANTIBODY SYNDROME

Deborah Dalmeida MD

Question 23

2 to 5-mm mm, red or purple macules (spots); in the distal lower extremities ,conjunctiva and palate

Deborah Dalmeida MD

Answer 23

Petechiae

Deborah Dalmeida MD

Question 24

Can you recall 2 examples of “inhibitors”

Deborah Dalmeida MD

Answer 24

Factor VIII antibodies (most common)

antiphospholipid antibodies

Deborah Dalmeida MD

Question 25

Consequence of microthrombi formation in DIC Deborah Dalmeida MD

Answer 25

tissue hypoxia and infarction Deborah Dalmeida MD

Question 26

**Give one word that describes this :** Circulating antibodies that destroy specific coagulation factors Deborah Dalmeida MD

Answer 26

Inhibitors ## Footnote Deborah Dalmeida MD

Question 27

Why do women with APLA have recurrent miscarriages? Deborah Dalmeida MD

Answer 27

Due to antibody-mediated **inhibition of t-PA activity** necessary for trophoblastic invasion of the uterus Deborah Dalmeida MD

Question 28

**1. What's your diagnosis?** Young adult, female Insidious onset of petechiae, ecchymoses BT- Prolonged Platelet count- Low PT - Normal PTT- Normal The bone marrow aspirate shows an increase in immature megakaryocytes 2. What are the antibodies detected? Deborah Dalmeida MD

Answer 28

1. Chronic Immune Thrombocytopenic Purpura (ITP) 2. autoantibodies directed against **platelet membrane glycoproteins IIb-IIIa or Ib-IX** Deborah Dalmeida MD

Question 29

Why is PT/INR used to monitor patients on warfarin? Deborah Dalmeida MD

Answer 29

Among all Vit K dependent coag factors Factor VII has the shortest half life. So if you give a patient Coumadin, the first factor to show a decrease in activity will be factor VII (the others will drop off too, but not until later on). it’s best to monitor therapy by taking a look at the extrinsic pathway (using the PT/INR), since that’s the pathway that will be affected first. Deborah Dalmeida MD

Question 30

Defect assoc with Glanzmann thrombasthenia Deborah Dalmeida MD

Answer 30

deficiency or dysfunction of glycoprotein IIb-IIIa Deborah Dalmeida MD

Question 31

cause of hemorrhage in DIC Deborah Dalmeida MD

Answer 31

depletion of factors required for hemostasis and the activation of fibrinolytic mechanisms Deborah Dalmeida MD

Question 32

Primary versus secondary antiphospholipid syndrome Deborah Dalmeida MD

Answer 32

**Primary antiphospholipid syndrome :** * manifestations of a hypercoagulable state * No evidence of other autoimmune disorders; * happens in association with certain drugs or infections. **Secondary antiphospholipid syndrome :** seen in individuals with a well-defined autoimmune disease, such as _systemic lupus erythematosus_ Deborah Dalmeida MD

Question 33

**Bernard Soulier/ vW disease?** BT- Prolonged **Platelet count-Normal** PT- Normal **PTT- Prolonged** reduced ristocetin cofactor activity which **normalizes after the addition of normal plasma** Deborah Dalmeida MD

Answer 33

vW disease Deborah Dalmeida MD

Question 34

Individual with known parenchymal liver disease ecchymoses, easy bruisability BT- Normal Platelet count- Normal PT- Prolonged PTT- Prolonged Fibrinogen - Normal **1. Diagnosis?** 2. **Name the special poikilocyte seen on the peripheral smear. What history given above explains its appearance on the smear?** Deborah Dalmeida MD

Answer 34

1. Vitamin K deficiency 2. Acanthocyte- if due to severe liver disease Deborah Dalmeida MD

Question 35

Very large, purpuric lesions Deborah Dalmeida MD

Answer 35

Ecchymoses Deborah Dalmeida MD

Question 36

Why do individuals with antiphospholipid antibodies exhibit prolonged PTT? ## Footnote Deborah Dalmeida MD

Answer 36

The autoantibodies also just happen to bind to the phospholipid part of the PTT reagent . Then there’s not enough usable reagent in the test tube, and the patient’s specimen doesn’t clot! The coagulation tests are therefore falsely prolonged. Deborah Dalmeida MD