PATH- 9-22 - ABNORMAL Hemostasis

Question 1

Thrombocythemia

Answer 1

When INC platelet count is a clonal proliferation and neoplastic.

Question 2

A: 7 Causes of Thrombocytopenia

B: List AT LEAST 2 examples of each

C: Quantitative or Qualitative Platelet Disorder?

Answer 2

Thrombo

Thrombocytopenia (low platelet count) = HHID BAD

1. Bone Marrow Alteration (marrow hypOplasia/aplasia/neoplastic replacement/leukemia)
2. Hereditary Thrombocytopenia (Fanconi’s anemia / [May Hegglin anomaly]
3. [Acquired Abnormal Hematopoiesis] (B12 Deficiency / PRE-Leukemia)
4. Drug induced ([Heparin - HIT] / Quinidine / Sulfonamides)
5. Dilutional (Hemodialysis / Heart-lung machine)
6. ITP and TTP (IgG Immune Thrombocytopenic purpura) and (Thrombotic Thrombocytopenic purpura)
7. HUS 2º to ESOH

Question 3

A: causes of Thrombocytosis: (3)

B: Normally Platelets are between _______ in the blood. During [Autonomous Thrombocythemia] platelets reach over a _______ as _______ and can occlude small _______

C: Quantitative or Qualitative Platelet Disorder?

Answer 3

causes of Thrombocytosis:

1) Splenectomy - platelets are normal in function
2) Reactive Thrombocytosis to CA/ Drugs/Infection
3) Autonomous Thrombocythemia = clonal disorder

B: Normally Platelets are between [200-500 K] in the blood. During [Autonomous Thrombocythemia] platelets reach over a million as [platelet clusters] and can occlude small vessels

C: Quantitative

Question 4

A: 3 Causes of QuaLitative Platelet Disorders

B: List 2 examples of each

Answer 4

1. Dz:(Multiple Myeloma / Liver Dz / paraproteinemia)
2. Drug: (Aspirin / NSAID)
3. Diet: ([Omega 3 Fatty Acids])

Question 5

Glanzmann’s thrombasthenia

B: Is this Autosomal Dominant or Recessive?

Answer 5

[GP-2b-3A] Defect that causes Aggregation defects and INC bleeding time

B: Autosomal recessive

Question 6

A: What Platelet dz is characterized by [GP1B/2A] defect, INC bleeding time and adhesion problems?

B: Autosomal Dom or Recessive?

Answer 6

A: Bernard-Soulier disease

B: Autosomal Recessive

Question 7

A: Storage Pool Dz

B: Gray Platelet Syndrome

Answer 7

A: Storage Pool Dz= DEC in [Dense Beta Granules] —> NO AGGREGATION

B: Gray Platelet Syndrome = Purpura development with no known origin

Question 8

Polycythemia vera

Answer 8

[Myeloproliferative disorder of Platelets] in which HCT is 60 (normal = 45)

Question 9

Vascular disorders are usually called ______ purpuras because these disorders do not result in ______

Platelet function and coagulation are ______.

C: 4 “shared” sx between Vascular Disorders and Platelet Disorders

Answer 9

Vascular disorders are usually called non-thrombocytopenic purpuras because these disorders do not result in severe bleeding diathesis.

Platelet function and coagulation are normal.

C:

Easy bruising,

• bleeding from mucosa,
• purpura,
• vasculitis

Question 10

5 Causes of Congenital SubEndothelial Disorders

Answer 10

1. Ehler Danlos Syndrome - Hypermobile joints and Hyper flexible skin,
2. osteogenesis imperfecta,
3. drugs,
4. infections,
5. amyloidosis

Question 11

5 Causes of Acquired SubEndothelial Disorders

Answer 11

1. Purpura simplex,
2. amyloids,
3. steroid purpura from prednisone
4. Cushing’s syndrome (steroid excess),
5. Henoch-Schonlin purpura (usually drug induced)

Question 12

A: _____ causes of Endothelial disorders is the most common. These include: (3)

vs.

B: _____\_ Endothelial Disorders come from: (2)

Answer 12

A: CONGENITAL cause of Endothelial disorders is the most common. These include:

1) [Hereditary Hemorrhagic Telangiectasia - HHT]
2) Arteriovenous malformation
3) [Giant Hemangioma from (Kasaback-Merritt syndrome)]

B: ACQUIRED Endothelial Disorders come from:

• Inflammation
• Vasculitits from Rickettsia / Drugs / Viruses

Question 13

Nutritional Disorder that can cause Abnormal Hemostasis

Answer 13

Scurvy (Vitamin C deficiency)

Question 14

A: Defects in [Clotting Factor 8] =_______

B: Defects in [Clotting Factor 9] = _______ or _______

C: BOTH result in _______ and are transmitted as [sex linked _______]

D: Labs for these will show INC _______ with no change in _______

Answer 14

A: Defects in [Clotting Factor 8] =Hemophilia A

B: Defects in [Clotting Factor 9] = Hemophilia B or [Christmas Disease]

C: BOTH result in Bleeding and are transmitted as [sex linked recessive]

D: Labs for these will show INC aPTT with no change in platelets

Question 15

A:

1. Which coagulation pathway does aPTT measure?
2. Which 4 factors are measured specifically?

B:

1. Which coagulation pathway does PT measure?
2. Which 5 factors are measured?

Answer 15

A: aPTT (intrinsic) –> 8, 9, 11 and 12 (actually measures all factors but 7, 13, protein C and S)

B: PT (extrinsic) [Thrombin Factor 2A], 5, 7, 10 and fibrinogen

Question 16

A: Mechanism of Von Willebrand’s Disease (2)

B: [Von Willebrand factor] binds to what 3 glycoprotein receptors on platelets?

C: Describe Type 1 and Type 3 Von Willebrand’s Disease

D: Describe Type 2 Von Willebrand’s Disease

E: How does this affect Bleeding Time? aPTT?

Answer 16

A: Hemostatic defect due to [von Willebrand (ristocetin co-factor) and (factor 8 antigen)].

B: [vWillebrand factor] binds to platelet receptors (glycoprotein 1b, 2b, 3a) AND to collagen and subendothelium.

C: Type-1 and Type-3 von Willebrand’s diseases are characterized by a decrease in the circulating level of the vWF.

D: Type-2 von Willebrand’s disease is characterized by a qualitative defect in the vWF

E: Bleeding Time WILL be Elevated with [mild aPTT elevation due to Factor 8 reduction]

Question 17

Hemophilia

A: Effect on Bleeding Time

B: Effect on aPTT

Answer 17

A: NO EFFECT ON BLEEDING TIME

B: aPTT is ELEVATED

Question 18

A: Describe Primary Fibrinolysis

A2: This condition is seen abnormally in _____ (AKA ____)

B: [Fibrinogen Degradation products] are actually _____ (pro vs. anti) coagulants.

B2: How do they do this? (3)

C: What does OD of thrombolytic agents cause?

Answer 18

A:

In primary fibrinolysis, fibrinogen is converted into [fibrinogen degradation products] by plasmin.

A2: This condition is seen in dead fetus syndrome (Abruptio Placenta)

B: [Fibrinogen Degradation products] are actually ANTI-coagulants by inhibiting:

• thrombin
• [platelet aggregation]
• Fibrin Cross-linking

C: OD of thrombolytic agents –> [1ºFibrinolytic State]—> Bleeding

Question 19

SECONDARY FIBRINOLYSIS (Mostly Caused by _______)

A: What occurs?

B: What does This results in?

C: What is a good lab indiciator for this state?

Answer 19

SECONDARY FIBRINOLYSIS (Mostly caused by Disseminated intravascular coagulation)

In secondary fibrinolysis both fibrin and fibrinogen are digested by plasmin.

B: This results in simultaneous digestion of clotting factors and consumption of platelets

C: D-Dimer levels are products of Fibrin breakdown and good indicator of DIC or [DVT/PE]

Question 20

Factor 5 Leiden

B: This Disease is the most common inherited cause of ________ state

Answer 20

Occurs when [Factor 5] is mutated to lack clevage site for Protein C and S DeActivation

B: This Disease is the most common inherited cause of hypercoagulable state

Question 21

Prothrombin 20210

Answer 21

Inherited Point mutation in ProThrombin resulting in INC gene expression —> INC Thrombin —> INC Thrombosis

Question 22

Hyperhomocysteinemia (4)

A: Etiology

B: Sx (4)

Answer 22

• CBS enzyme normally converts Homocysteine—> cystathionine
• When CBS is deficient, Homocysteine accumulates and causes:

B: “Fuck My Trashy Life…I have CBS problems smh”

1. Fingers that are slender and long
2. Mental Retardation
3. Thrombosis
4. Lens Dislocation