TEST 2: Coagulation

Question 1

Virchow Triad

Answer 1

Venous stasis, vessel damage, hypercoagulable state (venous thrombus formation)

Risk factors: age, obesity, pregnancy, cancer, surgery, trauma, prolonged immobilization, genetic hypercoagulable states, meds like oral contraceptives or hormone replacement therapy

Question 2

Idiopathic (or Immune) Thrombocytopenic Purpura (ITP)

Mechanism, Symptoms & NOTES

Answer 2

Mechanism: antibodies target and destroy platelets-> thrombocytopenia

Symptoms: Purpura, petechiae, mucosal bleeding, bruising.

Notes: more common in females, can affect kids and adults

Question 3

Idiopathic (or Immune) Thrombocytopenic Purpura (ITP)

Labs & treatment

Answer 3

Labs: coagulation is usually normal, just low platelet count (< 100k), R/O other causes HIV/Hep C etc first.

Treatment: Observe if no bleeding, corticosteroids, IVIG, Rituximab or thrombopoietin, if intractable splenectomy.

Question 4

Idiopathic (or Immune) Thrombocytopenic Purpura (ITP)

Primary vs. Secondary

Answer 4

Primary vs. Secondary: primary is isolated thrombocytopenia with no identifiable cause, as a diagnosis of exclusion from all other possible causes leaving autoimmune.

Secondary thrombocytopenia associated with a specific identifiable underlying condition or trigger ex. Viral infection, malignancy, other autoimmune diseases, or some drugs.

Question 5

Thrombotic Thrombocytopenic Purpura (TTP)

Mechanism & Symptoms

Answer 5

Mechanism: severe deficiency of ADAMTS13 (enzyme that acts on von Willebrand factor) can be secondary to genetic mutations (Upsaw-Schulman Syndrome) or more commonly antibodies that inhibit that enzyme.

Symptoms: predictable symptoms stemming from thrombocytopenia, hemolytic anemia, renal dysfunction, and fever.

Question 6

Thrombotic Thrombocytopenic Purpura (TTP)

Labs & treatment

Answer 6

Labs: Severely reduced activity of ADAMTS13 or antibody against it, thrombocytopenia, low Hgb, high LDH, high indirect bilirubin, high reticulocyte count, normal coagulation tests.

Treatment: Plasmapheresis (first line), corticosteroids, rituximab

Question 7

Hemophilia A

Mechanism & symptoms

Answer 7

Mechanism: Factor VIII deficiency, mutation in the F8 gene

Symptoms: bleeding of knees, elbows, ankles, GI. If mild bleeding will only occur after injury/trauma/surgery. If severe spontaneous bleeding can occur.

Question 8

Hemophilia A

Labs & GEMS

Answer 8

 Labs: Normal plts, normal PT, abnormal aPTT, low factor VIII

EARLY SIGNS IN CHILDREN: easy bruising, swelling, joint redness, mouth bleeding.

By age 3-4 most kids will have experienced an episode of excessive bleeding.

Boys can often be circumcised without excessive bleeding, but this does not guarantee the absence of hemophilia.

Question 9

Hemophilia B (Christmas Disease)

Mechanism & Symptoms

Answer 9

Mechanism: Factor IX deficiency, mutation in the F9 gene

Symptoms: bleeding of knees, elbows, ankles, GI. If mild bleeding will only occur after injury/trauma/surgery. If severe spontaneous bleeding can occur.

Question 10

Hemophilia B (Christmas Disease)

Labs & GEMS

Answer 10

Labs: normal plts, normal PT, abnormal aPTT, low factor IX.

Gems: EARLY SIGNS IN CHILDREN: easy bruising, swelling, joint redness, mouth bleeding.

By age 3-4 most kids will have experienced an episode of excessive bleeding.

Boys can often be circumcised without excessive bleeding, but this does not guarantee the absence of hemophilia

Question 11

Disseminated Intravascular Coagulation (DIC)

What is it, causes, mechanism

Answer 11

What: not a disease itself but a secondary effect of other medical conditions, leading to both excessive bleeding and clotting.

Causes: infection (sepsis), cancer, severe preeclampsia, placental abruption, trauma (TBI, burns, massive injury), ARDS, rhabdomyolysis, venomous snake bites, shock states, acidosis, hypoxia, fulminant liver failure, severe pancreatitis, transfusion reactions, or recreational drug use.

Mechanism: starts with endothelial damage activating clotting, simultaneously fibrinolytic system is activated, coagulation factors get depleted causing bleeding, the widespread clotting causes micro-thrombi systemically causing organ dysfunction from the disrupted blood flow.

Question 12

Disseminated Intravascular Coagulation (DIC)

Symptoms, labs, treatment

Answer 12

Symptoms: diffuse bleeding at multiple sites with minimal trauma, petechiae, large areas of ecchymosis, organ hemorrhage, stroke, PE, necrotic skin lesions, multisystem failure, blue finger/toe syndrome

Labs: high PT/PTT, low fibrinogen, high d-dimer, low platelets

Treatment: Fix underlying cause, blood products, anticoagulants, supportive care.

Question 13

Thrombus vs. embolus vs. thromboembolism

Answer 13

thrombus is any clot that forms in a blood vessel

embolus is a thrombus or any other debris that breaks free and travels through the blood stream

thromboembolism is a general term for traveling clots

Question 14

DVT

Provoked vs unprovoked

why proximal is important?

Answer 14

Provoked: due to a known risk factor

Unprovoked: occurs without any identifiable risk factor

Proximal DVT: Femoral or iliac veins, considered more dangerous than smaller veins due to size, higher risk of complications (PE etc.) and increased risk of recurrence.

Question 15

Protein C Deficiency

Result
Mechanism
Symptoms
GEMS

Answer 15

Result: natural anticoagulant

Mechanism: Inherited: (autosomal dominant) causing reduced production. Acquired: severe liver disease, DIC, warfarin

Symptoms: DVT/PE, warfarin induced necrosis

GEMS: higher risk with pregnancy, oral contraceptive, cancer, IBS

Question 16

Protein S Deficiency

Result
Mechanism
Symptoms

Answer 16

Results: is a Cofactor for Protein C enhancing the anticoagulant effect, therefore deficiency leads to excess clotting

Mechanism: Inherited: (autosomal dominant mutation), reduced production

Symptoms: DVT/PE, recurrent miscarriages

Question 17

Factor V Leiden

Mechanism
Symptoms
GEM

Answer 17

Mechanism:
only inherited, point mutation on factor V gene making factor Va resistant to inactivation by protein C

Symptoms: DVT/PE/Stroke

GEM: most common inherited hypercoagulable state

Question 18

Antiphospholipid antibody syndrome

What it is and GEMS

Answer 18

Acquired autoimmune syndrome where antibodies attack plasma proteins and clotting factors

GEMS: More common in women, commonly discovered after multiple miscarriages, results in many pregnancy complications

Question 19

3 Methods of Hemostasis

Answer 19

Vascular spasm (vasoconstriction)

Platelet plug

Coagulation cascade

Question 20

Primary hemostasis vs Secondary hemostasis

Answer 20

Primary hemostasis= platelet plug,

Secondary hemostasis= intrinsic/extrinsic/common pathway

Question 21

Intrinsic Pathway

What it is
Significant points
Clinical relevance

Answer 21

WHAT: activation is essential for maintaining hemostasis and preventing excessive bleeding when VESSELS ARE DAMAGED.

Significant:
started when a specific factor comes into contact with exposed collagen in a vessel wall (or negatively charged surface).

Uses many clotting factors culminating in Xa, Joins the COMMON pathway

Clinical Relevance:
deficiencies in intrinsic pathway factors (of which there are several) can lead to bleeding disorders such as Hemophilia A & B.

Question 22

Extrinsic Pathway

What it is
Significant points
Clinical relevance

Answer 22

WHAT: typically triggered by external trauma causing blood to exit the vascular system.

Significant points:
Started with exposure to Tissue factor outside the blood stream

Also joins the COMMON pathway at factor Xa

Clinical relevance: Different starting point i.e. physical trauma, dysregulation can result in bleeding or thrombotic conditions.

Question 23

Common Pathway

What it is
Significant points
Clinical relevance

Answer 23

What: End of intrinsic and extrinsic pathways

Significant Points: where anticoagulation mechanisms work. Examples: tissue factor pathway inhibitor, antithrombin III, protein C & S

Xa converts prothrombin to thrombin -> fibrinogen becomes fibrin -> reinforcement of platelet plug.

Clinical Relevance: Both intrinsic and extrinsic pathways lead to the common pathway where clotting and inhibition of clotting occur.

Question 24

Prothrombin Time (PT)

What does it assess?
Clinical Significance?

Answer 24

Assess: assess extrinsic and common pathway

Prolonged could indicate deficiencies in factors, liver disease, vit K def., or anticoagulation therapy.

Question 25

Activated Partial Thrombin Time (aPTT)

What does it assess?
Clinical Significance?

Answer 25

assess intrinsic and common pathway

Prolonged could indicate hemophilia, von Willebrand, heparin therapy, and presence of certain inhibitors (lupus anticoagulant)

Question 26

Fibrinogen

What does it assess?
Clinical Significance?

Answer 26

converted to fibrin by thrombin in last step of coagulation cascade making stable clot

Low may indicate DIC, liver disease or conditions that cause fibrinolysis

High may indicate acute phase reactions, inflammation, pregnancy, or some cancers.

Question 27

ASA

Answer 27

minimal effect on coagulation, mostly antiplatelet

Question 28

Clopidogrel

Answer 28

primarily targets platelet function

Question 29

Low Molecular Weight Heparin

Answer 29

enhances antithrombin activity (inhibits thrombin and factor Xa)

Question 30

Factor Xa Inhibitors (ex. Apixaban)

Answer 30

decreased conversion of prothrombin to thrombin

Question 31

Direct thrombin inhibitor (ex. Argatroban)

Answer 31

direct inhibition of thrombin preventing fibrinogen converting to fibrin.