Coagulopathy

Question 1

Prolonged activated Partial Thromboplastin Time (aPTT)

Genetic

Answer 1

Hemophilia A/B

(X-linked)

Hemophilia A prolonged A PTT

Question 2

Prolonged aPTT

Prolonged Bleeding time

Answer 2

vWF deficiency

intrinsic (8, 9, 11, or 12) pathway defect

Question 3

Prolonged PT, aPTT, Bleed Time

Low Platelets

Answer 3

DIC

Question 4

Prolonged Bleed time

Answer 4

Uremic platelet dysfunction

Question 5

Prolonged aPTT

Answer 5

Heparin

Question 6

Prolonged aPTT

Low Platelets

Answer 6

HIT

Question 7

Prolonged Prothrombin (PT)
slightly elevated aPTT (if at all)

Answer 7

Warfarin

Question 8

Low Platelets

Answer 8

Immune Thrombocytopenia

Question 9

↓ ADAMTS-13 level →
uncleaved vWF multimers →
platelet trapping & activation

Acquired (autoantibody) or hereditary

Answer 9

Thrombotic thrombocytopenic purpura

TTP

Question 10

↑ bilirubin ↑ LDH, ↓ haptoglobin ↑ bleeding time
↓ Platelets, schistocytes, Petichiae
↑ creatinine

Answer 10

Thrombotic thrombocytopenic purpura

TTP

Question 11

Diffuse microvascular thrombosis, causing microangiopathic hemolytic anemia

Answer 11

Thrombotic thrombocytopenic purpura

TTP

Question 12

Vascular damage & microthrombi formation

From Shiga toxin or Escherichiacoliserotype O157:H7

Answer 12

Hemolytic uremic syndrome

Question 13

↑ bilirubin ↑ LDH, ↓ haptoglobin ↑ bleeding time
↓ Platelets, schistocytes, Petichiae
Acute kidney injury (↑ BUN, ↑ creatinine)

Answer 13

Hemolytic uremic syndrome

Preceding bloody diarrhea

Question 14

DIC is marked by the excessive activation of the _______ coagulation cascade, leading to the generation of thrombin and cross-linked fibrin clots.

______ is then activated to clear the intravascular thrombi; plasminogen is converted to plasmin, which _________ and generates fibrin-degradation products (eg, elevated D-dimer).

Other anticoagulant proteins (eg, protein C, protein S) are also rapidly consumed.

Answer 14

extrinsic (tissue factor)

Fibrinolysis

cuts the cross-linked fibrin-fibers
(Plasmin Pierces Fibrin)

Question 15

Exertional heat stroke (extreme hyperthermia) and seizures increase the risk of ___

Answer 15

DIC

Question 16

vWD is inherited in an autosomal dominant fashion with ________ and is the most common heritable bleeding disorder.

Answer 16

variable penetrance

Question 17

Direct factor Xa inhibitors (eg, apixaban) are anticoagulants that block the ______ of factor Xa, which leads to reduced conversion of ___ to ____.

Answer 17

active site

prothrombin to thrombin

Question 18

Warfarin inhibits vitamin K epoxide reductase, which decreases the _____ form of vitamin K and limits _____ of vitamin K–dependent coagulation factors (II, VII, IX, X).

Answer 18

reduced

gamma-carboxylation

Question 19

Cimetidine, amiodarone, and TMP-SMX are CYP P450 inhibitors which ______, thus increasing the risk of ______.

Answer 19

Lowers warfarin metabolism (increases it’s effect)

bleeding

Question 20

Abnormal bleeding in patients with uremia (Pt on Dialysis or with CKD/ESR disease) is due to a qualitative platelet disorder that causes prolonged ______ only!

Answer 20

bleeding time

Question 21

Absent or ↓ factor ___ (hemophilia A)

Absent or ↓factor ___ (hemophilia B) activity

Answer 21

8 (Hemophilia 8-Ate)

9

Question 22

Slow oozing blood after mild trauma
Hemarthrosis, intramuscular hematomas
GI/GU bleeding
Intracranial hemorrhage

Answer 22

Hemophilia A/B
(intrinsic Pathways defect)
Complications: hemophilic arthropathy

Question 23

Low haptoglobin is a sign of

Answer 23

hemolytic anemia

Other associated findings include increased indirect bilirubin and lactate dehydrogenase.

Question 24

Signs of ______ include easy bruisability, petechiae, and mucocutaneous hemorrhage (eg, recurrent epistaxis, gingival hemorrhage).

Answer 24

thrombocytopenia

Question 25

PT reflects the _____ clotting pathway, which involves _____, fibrinogen, and factors II, V, VII, and X.   

Answer 25

extrinsic tissue factor

Question 26

_____ causes dusky discoloration of the skin (similar to cyanosis), and because it is unable to carry oxygen, a state of functional anemia is induced.  However, the blood ____ of oxygen will be unchanged as it is a measure of oxygen dissolved in plasma and is unrelated to hemoglobin function.

Answer 26

Methemoglobinemia partial pressure of O2

Question 27

_____ is an intracellular iron-storage protein that is used as a serum marker of total body iron stores.

Answer 27

Ferritin

Question 28

Hypersegmented neutrophils are characteristic of _______, which can be caused by folate and vitamin B12 deficiency.

Answer 28

megaloblastic anemias

Question 29

Etoposide is a chemotherapeutic agent that inhibits the sealing activity of _________.  Treatment causes chromosomal breaks to accumulate in dividing cells, as double stranded DNA fragments, ultimately causing cell death.

Answer 29

topoisomerase 2

Question 30

Prolonged Bleed time | Low Platelets

Answer 30

TPP

Question 31

warfarin-induced ______, a rare complication that can occur in individuals with underlying protein C or S deficiency shortly after starting warfarin.

Answer 31

skin necrosis *result in thrombotic occlusion of the microvasculature with skin necrosis.

Question 32

warfarin-induced skin necrosis a rare complication that can occur in individuals with underlying ________ shortly after starting warfarin.

Answer 32

protein C or S deficiency

Question 33

Many Caucasians have ____, which is modified to resist activated protein C.  The resulting hypercoagulable state predisposes to deep vein thromboses

Answer 33

factor V Leiden

Question 34

Many Caucasians have factor V Leiden which is modified to resist activated protein C.  Consequences of the hypercoagulable state predisposes to ____ & ____

Answer 34

deep vein thromboses & PE

Question 35

_____ is a plasma cell neoplasm associated with the overproduction of monoclonal immunoglobulins.

Answer 35

Multiple myeloma

Question 36

Serum protein electrophoresis demonstrates a monoclonal spike in the gamma globulin region and abnormal plasma cells. Diagnosis

Answer 36

Multiple myeloma

Question 37

Multiple myeloma is treated with medications that block _____ activity (eg, bortezomib) or increase _______ of specific transcription factors like Lenalidomide.

Answer 37

proteasome ubiquitination Lenalidomide increases E3 ubiquitin ligase binding to transcription factors overexpressed causing increased transcription factor destruction by the proteosome and cancer cell death.

Question 38

Give a pregnant women, _________ if she has thrombosis since it can't cross placenta. pregnancy makes you hypercoagulable

Answer 38

LMW Heparin (Enoxaparin)

Question 39

_______ rapidly reverses warfarin's effects whereas vitamin K requires time for clotting factor re-synthesis.

Answer 39

Fresh frozen plasma

Question 40

A normal bleeding time indicates adequate _______ function. 

Answer 40

platelet hemostatic

Question 41

A normal activated partial thromboplastin time (aPTT) indicates an intact ______ coagulation system. 

Answer 41

intrinsic

Question 42

Prolonged prothrombin time in the setting of normal aPTT indicates a defect in the extrinsic coagulation system at a step that is _______-.

Answer 42

not shared with the intrinsic system aka Factor 7 deficiency

Question 43

Factor XI deficiency results in a rare autosomal recessive disorder called ______.  Affected patients are at increased risk for bleeding following surgery or trauma.  prolonged aPTT normal PT.

Answer 43

hemophilia C

Question 44

How is desmopressin able to stop prolonged bleeding in Hemophilia A and Type-1 vWb Disease (2)

Answer 44

Increases circulating factor VIII | Increases endothelial secretion of vWF to stop bleeding

Question 45

Hemophilia B must be treated with

Answer 45

factor 9 replacement

Question 46

The thrombin time (TT) is prolonged with medications that directly or indirectly inhibit ______. 

Answer 46

thrombin

Question 47

________ inhibitors prolong both aPTT and PT with no effect on TT.

Answer 47

Direct factor Xa

Question 48

_________ inhibitors directly inhibit platelet activity and have little overall effect on aPTT, PT, or TT.

Answer 48

Cyclooxygenase (Asprin)

Question 49

_____ prevent the formation of thrombin (factor IIa), resulting in prolongation of aPTT, PT, and TT.

Answer 49

Direct thrombin inhibitors | dabigatran

Question 50

Factor 2a is also known as Factor 2 is aka

Answer 50

Thrombin Prothrombin

Question 51

_________ binds to antithrombin and causes inactivation of several coagulation factors, most significantly factor IIa (thrombin) and factor Xa.  aPTT and TT are prolonged

Answer 51

Unfractionated heparin

Question 52

Unfractionated heparin binds to antithrombin and causes inactivation of several coagulation factors, most significantly _____ and ______. 

Answer 52

``` factor IIa (thrombin) factor Xa ```

Question 53

Patients with cystic fibrosis are at risk for fat-soluble vitamin (ie, A, D, E, K) deficiency due to fat malabsorption from pancreatic insufficiency which can cause a _____PT and ______aPTT

Answer 53

Vitamin K deficiency thus prolonged PT normal aPTT

Question 54

Total body vitamin K does not contribute to a delay in warfarin efficacy.  However, increased intake of _______ can lead to subtherapeutic INR due to increased vitamin K availability in the liver.

Answer 54

foods rich in vitamin K (eg, green leafy vegetables)

Question 55

Nephrotic syndrome is a hypercoagulable state which can cause renal vein thrombosis. Loss of _____, is responsible for the thrombotic complications

Answer 55

antithrombin III

Question 56

_________- is a protein released from the alpha granules of platelets that plays a role in platelet aggregation.  It also binds heparin and helps inactivate the molecule. 

Answer 56

Platelet factor 4 (PF4)

Question 57

Heparin-induced thrombocytopenia and thrombosis results from the production of IgG antibodies against _______.  The Fc component of these antibodies binds to platelets, resulting in widespread platelet activation (prothrombotic state) & splenic destruction of these platelets (Thrombocytopenia)

Answer 57

complexes of heparin and platelet factor 4.