Hem & Onc - Pathology (Coagulation & platelet disorders, Hereditary hypercoagulability, & Blood transfusion therapy)

Question 1

Which coagulation pathways and factors does PT test?

Answer 1

Tests function of common and extrinsic pathway (i.e., factors I, II, V, VII, and X)

Question 2

Which coagulation pathways and factors does PTT test?

Answer 2

Tests function of common and intrinsic pathway (all factors except VII and XIII)

Question 3

In general, what kind of defect causes Hemophilia A or B? What are the specific defects?

Answer 3

Both intrinsic pathway coagulation defects; A: deficiency of factor VIII –> increased PTT; B: deficiency of factor IX –> increased PTT

Question 4

What are the PT and PTT trends in Hemophilia A or B?

Answer 4

PT normal, PTT increased

Question 5

What are the symptoms associated with Hemophilia A or B?

Answer 5

Macrohemorrhage in hemphilia - hemarthroses (bleeding into joints), easy bruising

Question 6

What is the lab finding associated with Hemophilia A or B?

Answer 6

increased PTT

Question 7

What is the treatment for hemophilia A?

Answer 7

Treatment: Recombinant factor VIII (in Hemophilia A)

Question 8

What are PT and PTT trends in Vitamin K deficiency? What is the bleeding time associated with Vitamin K deficiency?

Answer 8

Both PT and PTT increase; Normal bleeding time

Question 9

What kind of defect does Vitamin K deficiency cause?

Answer 9

General coagulation defect

Question 10

Vitamin K deficiency decreases the synthesis of what substances?

Answer 10

Decrease synthesis of factors II, VII, IX, X, protein C, protein S

Question 11

What causes an increased bleeding time?

Answer 11

Defects in platelet plug formation –> increased bleeding time (BT)

Question 12

Name 3 effects of platelet abnormalities.

Answer 12

Platelet abnormalities –> (1) microhemorrhage: mucus membrane bleeding, epistaxis, petechiae, purpura, (2) increased bleeding time, (3) possible decreased platelet count (PC)

Question 13

Give 4 examples of microhemorrhage that may occur as a result of platelet abnormalities.

Answer 13

microhemorrhage: mucus membrane bleeding, epistaxis, petechiae, purpura

Question 14

What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Bernard-Soulier syndrome?

Answer 14

PC decreased, BT increased

Question 15

In general, what kind of defect is Bernard-Soulier syndrome? What is the specific defect, and what causes it?

Answer 15

Defect in platelet plug formation; Decreased GpIb –> defect in platelet-to-vWF adhesion

Question 16

In general, what kind of defect is Glanzmann thrombasthenia? What is the specific defect, and what causes it?

Answer 16

Defect in platelet plug formation; Decreased GpIIb/IIIa –> defect in platelet-to-platelet aggregation

Question 17

What lab finding is associated with Glanzmann thrombasthenia?

Answer 17

Labs: blood smear shows no platelet clumping

Question 18

What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Glanzmann thrombasthenia?

Answer 18

PC = no change, BT increased

Question 19

What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Immune thrombocytopenia?

Answer 19

PC decreased, BT increased

Question 20

What is the specific defect in Immune thrombocytopenia, and what effect does it have?

Answer 20

Defect: anti-GpIIb/IIIa antibodies –> splenic macrophage consumption of platelet/antibody complex.

Question 21

What may trigger Immune thrombocytopenia?

Answer 21

May be triggered viral illness.

Question 22

How are platelets affected in Immune thrombocytopenia?

Answer 22

Decreased platelet survival

Question 23

What lab finding is associated with Immune thrombocytopenia?

Answer 23

Labs: Increased megakaryocytes on bone marrow biopsy

Question 24

What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Thrombocytic thrombocytopenic purpura?

Answer 24

PC decreased, BT increased

Question 25

What is the specific defect in Thrombocytic thrombocytopenic purpura, and what effect does it have?

Answer 25

Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) --> decreased degradation of vWF multimers

Question 26

What is the pathogenesis of Thrombocytic thrombocytopenic purpura?

Answer 26

Pathogenesis: increased large vWF multimers --> increased platelet adhesion --> increased platelet aggregation and thrombosis

Question 27

How are platelets affected in Thrombocytic thrombocytopenic purpura?

Answer 27

Decreased platelet survival

Question 28

What are 2 lab findings associated with Thrombocytic thrombocytopenic purpura?

Answer 28

Labs: schistocytes, increased LDH

Question 29

What are the symptoms associated with Thrombocytic thrombocytopenic purpura?

Answer 29

Symptoms: pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia

Question 30

What is the treatment for Thrombocytic thrombocytopenic purpura?

Answer 30

Treatment: exchange transfusion and steroids

Question 31

What are the changes to the following values in von Willebrand disease: (1) PC (2) BT (3) PT (4) PTT?

Answer 31

(1) No change (2) Increased (3) No change (4) No change or Increased

Question 32

What are the changes to the following values in DIC: (1) PC (2) BT (3) PT (4) PTT?

Answer 32

(1) Decreased (2) Increased (3) Increased (4) Increased

Question 33

What are the defects associated with von Willebrand disease, and what effects do they have?

Answer 33

(1) Intrinsic pathway coagulation defect: decreased vWF --> normal or increased PTT (depends on severity; vWF acts to carry/protect factor VIII). (2) Defect in platelet plug formation: decreased vWF --> defect in platelet-to-vWF adhesion.

Question 34

How severe is von Willebrand disease, and how common is it?

Answer 34

Mild but most common inherited bleeding disorder.

Question 35

What is the mode of inheritance of von Willebrand disease?

Answer 35

Autosomal dominant

Question 36

How is von Willebrand disease diagnosed?

Answer 36

Diagnosed in most cases by ristocetin cofactor assay (decreased agglutination is diagnostic)

Question 37

What is the treatment for von Willebrand disease, and how does it work?

Answer 37

Treatment: DDAVP, which releases vWF stored in endothelium

Question 38

What is the pathogenesis of DIC?

Answer 38

Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state.

Question 39

What are 7 causes of DIC?

Answer 39

Causes: (1) Sepsis (gram-negative) (2) Trauma (3) Obstetric complications (4) acute Pancreatitis (5) Malignancy (6) Nephrotic syndrome (7) Transfusion; Think: "STOP Making New Thrombi"

Question 40

What are 5 lab findings associated with DIC?

Answer 40

Labs: (1) schistocytes (2) increased fibrin split products (D-dimers) (3) decreased fibrinogen (4) decreased factors V and (5) VIII

Question 41

What is the most common cause of inherited hypercoagulability in whites?

Answer 41

Factor V Leiden

Question 42

What causes Factor V Leiden, and what is its effect?

Answer 42

Production of mutant factor V that is resistant to degradation by activated protein C

Question 43

Where is the Prothrombin gene mutation, and what effects does it have?

Answer 43

Mutation in 3' untranslated region --> increased production of prothrombin --> increased plasma levels and venous clots

Question 44

What effects does inherited Antithrombin deficiency have versus not have?

Answer 44

Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration.

Question 45

What are 4 hereditary thrombosis syndromes leading to hypercoagulability?

Answer 45

(1) Factor V Leiden (2) Prothrombin gene mutation (3) Antithrombin deficiency (4) Protein C or S deficiency

Question 46

What is the cause and effect of acquired Antithrombin deficiency?

Answer 46

Can also be acquired: renal failure/nephrotic syndrome --> antithrombin loss in urine --> increased factors II and X

Question 47

What effect does Protein C or S deficiency have?

Answer 47

Decreased ability to activate factors V and VIII

Question 48

For what outcome does Protein C or S deficiency increase the risk, and in what context?

Answer 48

Increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin

Question 49

If a patient has skin and subcutaneous tissue necrosis after Warfarin administration, what condition should be on the differential diagnosis?

Answer 49

Skin and subcutaneous tissue necrosis after warfarin administration --> think protein C deficiency.; Think: "Protein C Cancels Coagulation"

Question 50

What are 4 types of blood transfusion therapy?

Answer 50

(1) Packed RBCs (2) Platelets (3) Fresh frozen plasma (4) Cryoprecipitate

Question 51

What is the dosage effect of blood transfusion therapy containing packed RBCs?

Answer 51

Increase Hb and O2 carrying capacity

Question 52

What is the dosage effect of blood transfusion therapy containing platelets?

Answer 52

Increase platelet count (increase ~5000/mm^3/unit)

Question 53

What is the dosage effect of blood transfusion therapy containing fresh frozen plasma?

Answer 53

Increase coagulation factor levels

Question 54

What is the dosage effect of blood transfusion therapy containing cryoprecipitate?

Answer 54

Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin

Question 55

What are 2 clinical uses of blood transfusion therapy containing packed RBCs?

Answer 55

(1) Acute blood loss (2) Severe anemia

Question 56

What is the general clinical use of blood transfusion therapy containing platelets? Give 2 specific examples of this use.

Answer 56

Stop significant bleeding (thrombocytopenia, qualitative platelet defects)

Question 57

What are 4 clinical uses of blood transfusion therapy containing fresh frozen plasma?

Answer 57

(1) DIC (2) Cirrhosis (3) Warfarin overdose (4) Exchange transfusion in TTP/HUS

Question 58

What is the clinical use of blood transfusion therapy containing cryoprecipitate?

Answer 58

Treat coagulation factor deficiencies involving fibrinogen and factor VIII

Question 59

What are 5 risks of blood transfusions?

Answer 59

Blood transfusion risks include (1) infection transmission (low) (2) transfusion reactions (3) iron overload (4) hypocalcemia (citrate is a calcium chelator) (5) hyperkalemia (RBCs may lyse in old blood units).

Question 60

Why is hypocalcemia a risk of blood transfusions?

Answer 60

Hypocalcemia (citrate is a calcium chelator)

Question 61

Why is hyperkalemia a risk of blood transfusions?

Answer 61

Hyperkalemia (RBCs may lyse in old blood units)