Pathology - S2B2 - Blood 4

Front 1

What are the 3 things involved in Primary Hemostasis?

Back 1

1. Vascular Wall = Endothelium and Subendothelial Collagen
2. Platelets
3. von Willebrand Factor

Front 2

What does Primary Hemostasis involve the formation of?

Back 2

Platelet plug

Front 3

Describe the formation of a Platelet Plug

Back 3

1. Injury ➞ exposure of Subendothelial Collagen
2. vWF binds to collagen
3. Platelet binds to vWF via Gp Ib = Platelet Adhesion
4. Platelet-Platelet binding via Fibrinogen and Gp IIb/IIIa = Platelet Aggregation

Front 4

What is Secondary Hemostasis?

Back 4

Coagulation cascade resulting in a cross-linked fibrin clot

Front 5

What comprises the Extrinsic Pathway?

Back 5

Tissue Factor (Thromboplastin)

Factor VII (7)

Front 6

What comprises the Intrinsic Pathway?

Back 6

Prekallikrein
HMWK
Factors 12, 11, 9, 8

Front 7

What comprises the Common pathway of coagulation?

Back 7

Factors 10, 5, 2 (Prothrombin), 1 (Fibrinogen)

Front 8

This Factor causes Fibrin stabilization by converting soluble fibrin monomers to insoluble fibrin and crosslinking fibrin

Back 8

Factor 13

Front 9

Explain how the Extrinsic Pathway can activate the Intrinsic pathway

Back 9

-Factor 7a can activate Factor 9 (which along with Factor 8a can activate Factor 10)
-When pathway is complete Thrombin can go back and activate Factor 8 (which along with Factor 9 activates Factor 10)

Front 10

What is the most global screening test for Primary Hemostasis? Explain it

Back 10

Bleeding time = puncture the skin with a needle and measure the time it takes for bleeding to stop
-Normal values = 2-7 min

Front 11

Describe the Platelet Function Analyzer (PFA)

Back 11

Tests Primary Hemostasis
- tests the functionalities of vWF and Platelets IN VITRO
-Downfall: doesn't test the vessel wall

Front 12

This is the test for the Extrinsic Pathway of coagulation

Back 12

Prothrombin Time (PT)
- tests factors 7, 10, 5, 2, 1

Front 13

This is teh test for the Intrinsic Pathway of coagulation

Back 13

Partial Thromboplastin Time (PTT)
- tests factors 12, 11, 9, 8 / 10, 5, 2, 1

Front 14

What is the use of PTT?

Back 14

follow patients who are taking Heparin

Front 15

What is PT used to monitor?

Back 15

Warfarin = Extrinsic Pathway

Front 16

Explain the D-dimer test

Back 16

Is a molecule that can only be formed from the degradation of cross-linked fibrin = specific for Fibrinolysis

Front 17

Explain the Fibrin Split Products (FSP) test

Back 17

detects fragments associated with plasmin degradation of Fibrinogen or Insoluble fibrin from fibrin clots = not as specific as D-dimer for detection of Fibrinolysis

Front 18

What factors does Warfarin therapy decrease the levels of?

Back 18

Factors 2, 7, 9, 10 = Vitamin K-dependent Factors

Front 19

How do you tell the difference between a Factor deficiency and the presence of an Inhibitor?

Back 19

-If you add normal plasma and a clot forms = Factor deficiency

-If you add normal plasma but a clot doesn't form = Inhibitor

Front 20

What 2 things could causes Vasculitis and result in bleeding?

Back 20

1. Infections
- meningococcemia, Infective Endocarditis, Rickettsioses

2. Drugs

Front 21

What 3 things could cause impaired collagen formation and a resultant bleeding disorder?

Back 21

1. Scurvy = Vitamin C deficiency, which is required for Collagen synthesis

2. Cushing syndrome = high levels of blood cortisol

3. Ehlers-Danlos Syndrome = defect in collagen synthesis

Front 22

What immune complex hypersensitivity disease could cause bleeding?

Back 22

Henoch-Schonlein purpura
-purpuric rash
-colicky abdominal pain
-polyarthralgia
-acute glomerulonephritis

**deposition of IgA in small blood vessels

Front 23

Explain how Hereditary Hemorrhagic Telangiectasia causes bleeding

Back 23

Autosomal dominant disorder characterized by DILATED, torturous blood vessels that have THIN walls and hence bleed

Front 24

Infiltration of blood vessels with what could cause bleeding

Back 24

Amyloid

Front 25

Define Thrombocytopenia

Back 25

decrease in the # of platelets
- normal = 150K - 400K

Front 26

Give 7 examples that could cause decreased production of Platelets

Back 26

1. Bone Marrow Failure
2. Drugs
3. Infection (HIV)
4. Megaloblastic Anemia = Folate or B12 deficiency
5. Paroxysmal Nocturnal Hemoglobinuria = acquired membrane defect in multipotent myeloid stem cells = loss of membrane proteins that inhibit complement lysis
6. Myelodysplastic syndromes
7. Marrow Infiltration = Leukemia

Front 27

Give 4 examples of Immunological destruction that would decrease Platelet Survivial and cause Thrombocytopenia

Back 27

1. Idiopathic Thrombocytic Purpura
2. SLE
3. Drugs -> Heparin
4. Infection (HIV)

Front 28

Give 3 examples of nonimmunologic destruction of platelets causing Thrombocytopenia

Back 28

1. Thrombotic Thrombocytopenic Purpura
2. DIC
3. Microangiopathic Hemolytic Anemia (MAHA)

Front 29

What organ can sequester Platelets and cause thrombocytopenia?

Back 29

Spleen

**Hypersplenism in Portal HTN

Front 30

Describe Dilution Thrombocytopenia

Back 30

Occurs in patients who have received massive transfusions and their platelet concentration is diluted enough to allow for bleeding

Front 31

What is the cause of Idiopathic (Immune) Thrombocytopenic Purpura (ITP)?

Back 31

Autoantibodies against GP Ib or IIb/IIIa

**usually IgG

Front 32

Describe the pathogenesis of ITP

Back 32

1. Anti-platelet Ab's
2. Platelet opsonization
3. Platelet destruction in the spleen
4. Thrombocytopenia

Front 33

What are the lab findings in Idiopathic Thrombocytic Purpura

Back 33

1. Prolonged Bleeding time/PFA = b/c platelets are affected

2. Normal PT/PTT = coagulation is not affected

Front 34

What are 4 pathologies associated with Idiopathic Thrombocytic Purpura?

Back 34

1. Thrombocytopenia with Megathrombocytes in peripheral blood
2. Anti-platelet Ab's
3. Splenic congestion of sinusoids and lymphoid hyperplasia
4. Increases BM Megakaryocytes

Front 35

Describe Chronic Idiopathic Thrombocytpic Purpura

Back 35

1. Most common in WOMEN <40
2. Mucocutaneous bleeding
-bleeds are in response to minor injuries

Front 36

Describe Acute Idiopathic Thrombocytic Purpura

Back 36

Occurs in children following a Viral infection
-abrupt onset of epistasis

Front 37

What are the treatments for Chronic Idiopathic thrombocytic purpura?

Back 37

1. Steroids
2. Immunosuppression
3. Splenectomy (chronic)

**Acute ITP is usually self-limited

Front 38

What are 4 drugs that commonly cause Drug-Induced Thrombocytopenia?

Back 38

1. Quinine = anti-malarial
2. Quinidine = antiarrhythmic agent
3. Sulfonamides
4. Heparin

Front 39

Describe Type 1 Heparin induced thrombocytopenia

Back 39

Mild thrombocytopenia
Common = 5% of patients on heparin

Front 40

Describe Type 2 Heparin-Induced Thrombocytopenia

Back 40

-Severe thrombocytopenia due to Ab's against Heparin-PF4 complex
-paradoxical risk of thrombosis due to platelet activation

Front 41

What 3 diseases does Thrombotic Microangiopathy comprise?

Back 41

1. Thrombotic Thrombocytopenic Purpura
2. DIC
3. Hemolytic Uremic Syndrome

Front 42

What is the underlying cause of Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome?

Back 42

deficiency of a vWF cleaving protease = ADAMTS 13 in TTP

Front 43

Describe the pathogenesis of TTP and HUS

Back 43

1. decreased vWF cleaving protease
2. Ultra-high molecular weight vWF multimers = spontaneously cause platelets to aggregate w/out endothelial injury
3. Platelet activation and consumption
4. Thrombocytopenia and microvascular thrombi (caused by platelet aggregates)

Front 44

What are the pathologic findings in HUS and TTP?

Back 44

1. Thrombocytopenia = due to the consumption of platelets by Platelet aggregates caused by HMW vWF

2. Schistocytes = due to platelet aggregates in the microvasculature -> RBC's bump into them and are sheered

3. Normal PT/PTT = coagulation cascade factors are not affected

Front 45

Describe the clinical features of Thrombotic Thrombocytopenic Purpura

Back 45

1. Adult women
2. Classic pentad
-Fever
-Neurologic deficits
-Microangiopathic Hemolytic anemia
-Thrombocytopenia
-Renal Failure

Front 46

Describe the clinical features of HUS

Back 46

1. CHILDREN (TTP = Adult women)
2. follows infection with Verotoxin producing EHEC
3. Renal failure predominates; neurologic findings absent

Front 47

What are the major differences between HUS and TTP?

Back 47

HUS = Children with Renal Failure predominance

TTP = Adult women with neurologic deficits (along with renal failure)

Front 48

What 2 clinical findings do HUS and TTP share?

Back 48

1. Microangiopathic Hemolytic anemia
2. Thrombocytopenia

Front 49

What is the treatment for both HUS and TTP?

Back 49

Plasma exchange = replenishes vWF cleaving protease while taking out the HMW vWF

Front 50

This is an Autosomal Recessive deficiency of GP Ib, which causes a platelet adhesion defect = platelets do not bind to vWF

Back 50

Bernard-Soulier Syndrome

Front 51

Autosomal Recessive deficiency of GP IIb/IIIa which causes a defect in Platelet Aggregation = platelets cannot bind to eachother via fibrinogen

Back 51

Glanzmann thrombasthenia

**Glanzmann - aGGregation

Front 52

What are the lab findings in both Bernard-Soulier syndrome and Glanzmann Thrombasthenia?

Back 52

1. Prolonged Bleeding Time / PFA

2. Normal PT/PTT

Front 53

What is the treatment for Bernard-Soulier syndrome and Glanzmann Thrombasthenia?

Back 53

Platelet transfusion

Front 54

What are 2 acquired disorders that can lead to platelet disorders and bleeding?

Back 54

1. Aspirin and other NSAIDS = COX inhibition and suppression of PG synthesis = inhibits TXA2 synthesis

2. Uremia = renal failure resulting in increased blood urea --> somehow affects platelets

Front 55

Immune Thrombocytopenic Purpura
- autoAb's to Gp Ib or IIb/IIIa
- Megathrombocyte seen in Blood Smear due to leakage from the BM

Back 55

What platelet disorder would cause this?

Front 56

Draw the Coagulation Cascade

Back 56

-

Front 57

HUS or TTP
-Schistocytes due to platelet consumption and intravascular thrombosis = RBC's are sheered by the platelet plugs

Back 57

What platelet disorder would cause this?

Front 58

A 32-year-old woman is brought to the emergency room by a friend b/c of the onset of confusion and disorientation over the past day. Upon physical exam, you discover generalized rash, fever, and bilateral Babinski sign. You immediately order several blood tests, which show an elevated LDH, increased indirect bilirubin, thrombocytopenia, and anemia. Examination of a peripheral blood smear yields multiple reticulocytes and schistocytes.

Back 58

Thrombotic Thrombocytopenic Purpura