Approach To Bleeding

Question 1

Unique characteristic of megakaryocytes.

Answer 1

Ability to continue DNA synthesis without undergoing mitosis.

Question 2

What signals pluripotent stem cells to form into platelets?

Answer 2

Some signal causes growth factors, mainly thrombopoietin from the kidney and liver to be released into blood. Thrombopoietin goes to the bone marrow and signals the CD34+ stem cells to differentiate into megakaryocytes.

Question 3

Function of GPIb-IX-V

Answer 3

Binds platelets to vWF

Question 4

Function of GPIa-IIa and GPVI

Answer 4

Bind platelets to collagen

Question 5

Function of GPIIb/IIIa

Answer 5

Binds fibrin. Allows platelets to bind each other.

Question 6

Name the 4 things in platelet alpha granules.

Answer 6

1. vWF
2. Factor V
3. Plasminogen Activator Inhibitor-1 (PAI-1)
4. Fibrinogen

Question 7

Name the 3 things found in platelet dense granules.

Answer 7

1. ADP/ATP
2. Serotonin
3. Calcium

Question 8

Location of Alpha-2 Antiplasmin

Answer 8

Bound to Factor XIIIa

Factor XIII crosslinks fibrin monomers to make a soft clot into a hard clot

Question 9

What is a mixing study?

Answer 9

Test done after both a prolonged PT and prolonged PTT. Patient’s blood is mixed with normal blood. If the either one corrects, the defect was a Factor deficiency. If neither correct, the defect is a Factor inhibitor.

Question 10

What is the minimum platelet count that is well-tolerated by the population?

Answer 10

10,000/uL

Question 11

What is the minimum platelet count that surgeons want to see before an operation?

Answer 11

50,000/uL

Question 12

Most common cause of Thrombocytopenia due to production defects.

Answer 12

Bone marrow is infiltrated by malignant cells. Interferes with normal stem cells to produce blood cells including megakaryocytes.

Question 13

Most common cause of Thrombocytopenia due to abnormal sequestration.

Answer 13

Hypersplenism: splenomegaly resulting from accumulation of blood products in the spleen.

Question 14

Pathology of DIC.

Answer 14

Disseminated Intravascular Coagulation
-some trigger simultaneously activates both thrombin and plasmin eliminating clotting factors rapidly. The result is both bleeding and microvascular thrombosis.

Question 15

In patients with DIC, what lab values are expected?

1. Platelets
2. PT
3. PTT
4. Fibrinogen
5. D-Dimers

Answer 15

1. Decreased (thrombocytopenia)
2. Increased
3. Increased
4. Decreased
5. (+) Test

Question 16

What is the D-dimer test?

Answer 16

D-dimers are a byproduct of plasmin degredation of fibrin monomer units in a clot.

Question 17

Tx for DIC.

Answer 17

• reverse underlying cause (infection, drugs etc)

- Replace platelets and coagulation factors

Question 18

Pathogenesis of TTP and HUS.

Answer 18

1. Activation of platelets causing microthrombi in small capillaries.
2. Ischemia to organs occurs, most commonly kidneys and brain (TTP)
3. Micro thrombi also cause lysis of RBCs as they rub across the thrombi at high velocity.

Question 19

Cause of platelet activation in Hemolytic Uremic Syndrome (HUS).

Answer 19

Damage to endothelial cells by the Shiga Toxin.

Question 20

Cause of platelet activation in TTP.

Answer 20

Large multimers of vWF accumulate due to lack of ADAMTS13 which normally cleaves them.

Question 21

What are the symptoms of HUS and TTP

Answer 21

Both: Thrombocytopenia, Renal Failure, hemolytic anemia

TTP only: fever, neurologic symptoms

Question 22

What labs are expected with HUS and TTP

1. Platelets
2. Bilirubin
3. LDH
4. Haptoglobin
5. PT
6. PTT
7. Blood Smear

Answer 22

1. Low
2. increased
3. Increased
4. decreased
5. normal
6. normal
7. shcistocytes

Question 23

Presentation of pre-Eclampsia and HELLP syndrome.

Answer 23

pre-Eclampsia: HTN, proteinuria, edema
HELLP: Hemolysis, Elevated Liver Enzymes, Low Platelets

Etiology of both unclear

Question 24

Tx of pre-Eclampsia and HELLP

Answer 24

Deliver baby

Question 25

Mechanism of Drug-Induced Immune Thrombocytopenia.

Answer 25

Some medication changes the surface epitope on platelets. This causes the body to recognize the platelets as “foreign” and Abs are produced to remove them.

Question 26

Mechanism of HIT.

Answer 26

Heparin Induced Thrombocytopenia

• heparin normally binds platelet factor 4 (PF4 or Antithrombin III) preventing its activation.
• the body recognizes the heparin-PF4 complex and activates platelets as an immune reaction causing clotting.

Question 27

Tx of HIT

Answer 27

Stop Heparin

Use direct thrombin inhibitors

Question 28

Pathogenesis of ITP.

Answer 28

Immune thrombocytopenic purpura

-autoAbs against platelets are produced.

Question 29

What lab values result from ITP

Answer 29

Only low blood count is platelets
Marrow biopsy shows megakaryocyte hyperplasia

(diagnosis of exclusion when all other causes are ruled out for thrombocytopenia. Skin has purpura)

Question 30

Tx for ITP.

Answer 30

Prednisone
IVIG (Intravenous IgG that recognizes the autoantibodies, binds them, and inactivates them)

Question 31

Defect in Glanzmann Thrombocytopenia.

Answer 31

Autosomal Recessive

GPIIb/IIIa defect

Question 32

Defect in Bernard Soulier Syndrome

Answer 32

Abnormal GPIb-IX-V protein

-giant platelets because of the GP role in megakaryocyte development

Question 33

Why don’t you give NSAIDs with ASA?

Answer 33

NSAIDs can interfere with the anti-platelet effect of ASA, potentially rendering aspirin less effective when used for cardioprotection and stroke prevention