Bleeding Disorders

Question 1

Primary hemostasis

Answer 1

Initial platelet plug

Question 2

Importance of vasoconstriction during hemostasis

Answer 2

Control platelets and other elements, slow blood, and apply sheer force

Question 3

Secondary hemostasis

Answer 3

Provides stable fibrin cross-linking

Question 4

Coagulation cascade

Question 5

Platelet activation

Answer 5

Rolling and binding to the subendothelium, recruitment of other coagulation factors,

Question 6

Platelet lineage

Answer 6

From megakaryocytes, creep out into blood vessels and break off in fragments as the platelets.

Question 7

Platelet structures

Answer 7

No nucleus
Electron dense- granules
α-granules

Question 8

Electron-dense granules

Answer 8

Secretory vesicles, typically 3–8 per platelet, high cation concentrations. They store high concentrations of small molecules—primarily ionized calcium, serotonin, ADP, ATP, and polyphosphates, released upon activation to initiate platelet aggregation.

Question 9

α-Granules contents

Answer 9

Fibrinogen, fibronectin, β-thromboglobulin, thromboxane.

Question 10

GPIa/IIa function

Answer 10

Receptor that binds collagen in the subendothelium

Question 11

GPIIb/IIIa function

Answer 11

Receptor for fibrinogen

Question 12

GPIb/IX/V function

Answer 12

Receptor that binds von Willebrand Factor bound in the subendothelium

Question 13

Role of platelets in hemostasis

Answer 13

Adhere to sites of vascular injury via collagen and vWF in the subendothelium.
Activation is the release of granules to recruit more platelets, leading to aggregation into the hemostatic plug and coagulation pathways.

Question 14

Primary hemostasis mechanism

Answer 14

Platelets bind collagen directly or via vWF.
Activation induced by binding leads to granule release.
Platelets aggregate together.

Question 15

Where are coagulation factors produced and were do they circulate?

Answer 15

Made in the liver and circulate in the blood as inactive precursors.

Question 16

How are coagulation factors activated?

Answer 16

Activate eachother in a cascade when in proximity on the phospholipid surface of platelets

Question 17

What molecules do coagulation factor precursors require and why?

Answer 17

Require calcium to undergo conformational changes into active forms. Calcium found in dense granules.

Question 18

Where does the intrinsic clotting pathway originate

Answer 18

Surface contact induces activation of factor XII

Question 19

Where does the extrinsic clotting pathway originate?

Answer 19

Tissue thromboplastin released from tissues and platelets, activation of factor VII

Question 20

Where does the common clotting pathway converge?

Answer 20

With the activation of factor X

Question 21

What is the final step in the common clotting pathway?

Answer 21

Formation of insoluble fibrin polymers in the presence of calcium and factor XIII

Question 22

What injuries can initiate a clot?

Answer 22

Mechanical traumas from too much injury.
Vessel wall weakness from cushings, congenital disorders, or scurvy.
Immune injury - vasculitis.

Question 23

Cushings as a vascular disorder

Answer 23

High cortisol increases clotting due to too much SE exposure.

Question 24

Scurvy as a vascular disorder

Answer 24

Vitamin C deficiency causes increased injury.

Question 25

Bernard Soulier Syndrome mechanism

Answer 25

Autosomal recessive disorder in which there is a deficiency of GpIb such that platelets cannot bind vWF.

Question 26

Bernard Soulier Syndrome characteristics

Answer 26

Abnormally large platelets, bleeding disorder.

Question 27

Bernard Soulier Syndrome treatment

Answer 27

Platelet transfusion

Question 28

Glanzmann thrombasthenia mechanism

Answer 28

Autosomal recessive disorder in which there is a defiiency of GpIIb/IIIa such that platelets cannot bind to fibrinogen

Question 29

Glanzmann thromboasthenia characteristics

Answer 29

Delayed inset bleeding disorder with variable severity

Question 30

Glanzmann thrombasthenia treatment

Answer 30

Only preventative such as hemodynamically stabilising someone prior to surgery. Only transfuse platelets if there has been a severe bleed and otherwise lifestyle adaptions.

Question 31

Platelet type von Willebrand Disease mechanism

Answer 31

Autosomal dominant disorder characterised y enhanced GpIb binding too avidly to vWF. Consumptive process in which large platelet aggregates then get removed from criculation resulting in thrombocytopenia and low free vWF.

Question 32

Platelet type con Willebrand Disease characteristics

Answer 32

Bleeding disorder with mucocutaneous bleeding (mouth, nose, uterine) and bleeding after surgery

Question 33

Treatment for PvWD

Answer 33

Platelet transfusions.

Question 34

Mechanism of hemophilia A

Answer 34

Factor VIII deficiency - disruption in the intrinsic pathway

Question 35

Mechanism of hemophilia B

Answer 35

Factor IX deficiency affecting intrinsic pathway

Question 36

Hemophilia complications

Answer 36

Prolonged/uncontrolled bleeding, bruising, muscle bleeding (deep hematomas), hemarthrosis.

Question 37

Hemophilia treatments

Answer 37

Treat with factor replacements an bleeding prevention.

Question 38

Factor replacements

Answer 38

Treatment of hemophilia with recombinant products to replace what is deficient.

Question 39

Von Willebrand Disease mechanism

Answer 39

Various deficiencies that may be quantitative or qualitative

Question 40

Various manifestations of vWD

Answer 40

Mucosal bleeding, epistaxis, easy bruising and petechia, excessive surgical bleeding, menorrhagia

Question 41

vWD disease type that is converse to PT-vWD

Answer 41

Type 2B - qualitative variants with increased affinity for platelets. Looks similar to PT-vWD but requires different treatments

Question 42

Complete deficiency of vWD looks like what other disorder?

Answer 42

Hemophilia A

Question 43

Amyloidosis mechanism

Answer 43

Acquired factor X deficiency that leads to amyloid protein deposits in the tissues.

Question 44

What does factor X stick to?

Answer 44

Amyloid fibrils, then it is removes from circulation.

Question 45

Characteristic symptom of amyloidosis

Answer 45

Raccoon sign

Question 46

Disseminated intravascular deficiency mechanism

Answer 46

Various traumas that lead to extensive consumption of clotting factors and plasmin (fibrinolysis). Huge activation of the cascade (everywhere) leads to consumption.

Question 47

Symptoms of DIC

Answer 47

Hemolysis due to shearing of RBCs by fibrin clots, uncontrolled bleeding.

Question 48

Treatment of DIC

Answer 48

Must address the underlying issue. DIC is a symptom, not a diagnosis.

Question 49

Warfarin

Answer 49

Anticoagulant that blocks vit K epoxide reductase to inhibit vitamin k dependent factors, lI, VII, IX, X.

Question 50

Heparin

Answer 50

Blocks factor X and II.

Question 51

Apixaban

Answer 51

Anti-Xa drugs

Question 52

Cons of warfarin

Answer 52

Cheap but relies on stable diets, and requires repeat blood work

Question 53

Factor V leiden

Answer 53

Inherited clotting abnormalities such that protein C cannot regulate factor V activity. Induces a pro-coagulant state.

Question 54

Protein C

Answer 54

Natural fibronolytic that controls clotting

Question 55

G20210A prothrombin gene mutation

Answer 55

Increased prothrombin mRNA stability. Increased thrombin levels induces a pro-coagulant state.