Bleeding Disorders 1

Question 1

What is the first question to ask when a patient has a bleeding disorder?

Answer 1

Is it a platelet problem? Or is it at coagulation problem?

Question 2

2 events of the first phase of hemostasis

Answer 2

1. Arterial vasoconstriction (endothelin mediated)
2. Platelet adhesion → formation of platelet plug

Question 3

Events of secondary hemostasis

Answer 3

1. Coagulation
2. Clot resorption

Question 4

Classification of bleeding disorders

Answer 4

1. Thrombocytopenia and platelet disorders
2. Coagulation defects
3. Fragility of vessel walls

Question 5

What 2 labs would you order to determine whether the problem is platelet sarcoid relation?

Answer 5

1. CBC
2. Coagulation tests: PT, PTT

Question 6

Normal number of platelets

Answer 6

150,000 to 400,000

Question 7

Below _____ = post-traumatic bleeding; below _____= spontaneous bleeding

Answer 7

• 50,000
• 20,000

(platelets can function from 50,000-150,000)

Question 8

Half-life of platelets

Answer 8

9 days

(2-3 if transfused)

Question 9

Intrinsic system of coagulation is activated by _____ and involve factors _____.

Answer 9

• Collagen exposure
• XII, XI, IX, X

Question 10

Regulation pathways converge at factor ______

Answer 10

X → Xa + V

Question 11

The extrinsic system of coagulation is activated by ______

Answer 11

external trauma tissue factor

Question 12

PT

Answer 12

Prothrombin time

Question 13

PT monitors the ____ pathways by measuring the ______.

Answer 13

• Extrinsic and common pathways
• clotting of plasma after thromboplastin & Ca²⁺ ions

Question 14

PTT monitors the _____ pathways by measuring the _____.

Answer 14

• intrinsic and common
• clotting of plasma after kaolin, cephalin & Ca²⁺ ions

Question 15

Factor V, X, prothrombin and fibrinogen are all measured in BOTH PT & PTT, which factors are specific to the PT pathway? PTT pathway?

Answer 15

• VII
• VIII, IX, XI, XII

Question 16

What is the main difference equation between platelets and coagulation problems clinically?

Answer 16

Platelet problems are mostly superficial bleeding

(skin & mucous sx)

Question 17

What is the difference between petechiae, purpura and ecchymoses?

Answer 17

• Petechiae: 1-2 mm
• Purpura: 2mm - 1 cm
• Ecchymoses: > 1cm

Question 18

These are typical of which type of general bleeding disorders?

Answer 18

Platelet disorders → superficial bleeding

Question 19

What is the biggest threat a platelet disorders?

Answer 19

Intracranial bleeding

(rare, but most serious)

Question 20

Once you determine the patient has a platelet dysfunction what is the next question to ask?

Answer 20

Too few platelets or defective platelets

Question 21

4 Causes of thrombocytopenia

Answer 21

1. Decrease survival
2. Decrease production
3. Sequestration
4. Dilution

(MC)

Question 22

Decrease production of platelets is commonly due to ______ (6).

Answer 22

1. Aplastic anemia
2. B12, folate deficiency
3. Drugs/EtOH
4. Infection
5. Leukemia
6. myelodysplastic syndrome (ineffective hematopoiesis)

Question 23

How does heparin cause decreased platelet production?

Answer 23

anti-heparin-PF4 ab → activate platelets & pro-thrombotic state → depletion

Question 24

List the drugs that can cause a decreased production of platelets (6).

Answer 24

1. Chemotherapy
2. Heparin
3. Quinidine
4. Radiotherapy
5. Sulfur compounds
6. Thiazides

Question 25

Why is concomitant thrombocytopenia a common problem in cancer patients \_\_\_\_\_\_\_?

Answer 25

1. Bleeding risk 2. Thrombocytopenia limits chemotherapy schedule

Question 26

In evaluating a thrombocytopenic cancer patient you must check for ______ (6).

Answer 26

1. Coagulopathy 2. Drug reactions 3. Infection 4. ITP 5. Post-transfusion purpura 6. TTP & HUS

Question 27

Which chemotherapy drugs have the highest rate of inducing thrombocytopenia (2)?

Answer 27

1. Gemcitabine 2. Platinum-based regimens

Question 28

How do the following chemotherapy agents → thrombocytopenia: 1. alkylating agents affect \_\_\_\_\_\_. 2. cyclophosphamide agents affect \_\_\_\_\_\_\_. 3. bortezomib prevents \_\_\_\_\_\_.

Answer 28

1. stem cells 2. later megakaryocyte progenitors 3. platelet release from megakaryocytes (some treatments promote platelet apoptosis)

Question 29

The main regulator of platelet production is ______ and is therefore used as a treatment for thrombocytopenic patients with cancer to receive chemo.

Answer 29

thrombopoietin

Question 30

Classical causes of thrombocytopenia (decreased survival of platelets)

Answer 30

1. ITP (immune thrombocytopenia) 2. TTP 3. HUS

Question 31

In ITP (immune thrombocytopenia), antibodies destroy the platelets. What are the secondary causes?

Answer 31

1. SLE 2. HIV 3. CLL

Question 32

In ITP, IgG anti-platelet antibodies opsonize the \_\_\_\_\_\_.

Answer 32

platelets → phagocytosis of platelets/megakaryocytes in the spleen (GpIIb/GpIIIa on platelets which mediates primary hemostasis)

Question 33

ITP is most commonly seen in which patient population

Answer 33

women under 40

Question 34

ITP s/sx

Answer 34

1. petechiae 2. mucosal bleeding (nose bleed, excessive bleeding from gums) 3. ecchymoses

Question 35

What is thrombotic thrombocytopenic purpura

Answer 35

excessive platelet activation → deposit as thrombi in small blood vessels

Question 36

Pentad for TTP

Answer 36

Mn: “Nasty Fever Ruined My Tubes” * N – Neurological symptoms, * F – Fever * R – Renal function impairment * M – Microangiopathic hemolytic anemia * T – Thrombocytopenia

Question 37

TTP is associated with an enzyme deficiency of ______ which leads to \_\_\_\_\_.

Answer 37

* ADAMTS13 (vWF metalloprotease) * vWF accumulate → platelet activation & aggregation (acquired auto-ab or inherited)

Question 38

TTP patients must avoid

Answer 38

transfusion of blood cells (especially platelets)

Question 39

TTP tx (3)

Answer 39

1. plasma transfusions (plasmapheresis) 2. ASA & persantine 3. prednisone (blood will increase the progression of disease)

Question 40

**Typical** HUS is caused by \_\_\_\_\_\_

Answer 40

shiga-like toxin of E. coli O157:H7

Question 41

In typical HUS, shiga-like toxin of E. coli O157:H7 damages \_\_\_\_\_.

Answer 41

endothelial cells, activates platelets → aggregation

Question 42

Symptoms of HUS

Answer 42

bloody diarrhea | (after HUS exposure)

Question 43

**Atypical** HUS is caused by \_\_\_\_\_

Answer 43

deficiency of alternative pathway complement inhibitor (CD46 or factor I) (inherited or acquired by antibody production)

Question 44

Atypical HUS may be triggered by _____ (4).

Answer 44

1. Rx 2. Radiation 3. Infection: HIV, pneumococcal 4. SLE, lymphoid neoplasms

Question 45

How do you distinguish from DIC & HUS?

Answer 45

1. TTP & HUS is a platelet problem 2. DIC is a coagulation + platelet problem (PT & PTT is normal in TTP & HUS)

Question 46

Answer 46

HUS: glomerulus w/capillary fibrin thrombi, karyorrhexis & entrapped fragmented RBCs

Question 47

Answer 47

HUS : Diffuse glomerular basement membrane multilayering (PAS staining)

Question 48

In addition to ITP, TTP & HUS, what are the 2 other causes of thrombocytopenia?

Answer 48

1. Sequestration of platelets in spleen 2. transfusions w/non-viable platelets → dilution

Question 49

Spleen findings in thrombocytopenia

Answer 49

normal size, but congested sinusoids & enlarged follicles

Question 50

bone marrow findings in thrombocytopenia

Answer 50

increased number of megakaryocytes

Question 51

peripheral blood findings of thrombocytopenia

Answer 51

megathrombocytes