Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

JAAD CME > 74(5) Coagulation Disorders > Flashcards

74(5) Coagulation Disorders Flashcards

1
Q

What are the inherited hypercoagulable states?

A
  1. Factor V Leiden Mutation
  2. Prothrombin G202120A Mutation
  3. Antithrombin III Deficiency
  4. Protein C and S Deficiencies
  5. Hyperhomocysteinemia
  6. Sickle Cell Disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the most common primary HS?

A

Factor V Leiden (affects 5-15% of pop)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Mechanism behind FVLM?

A

Mutated FVa is resistant to degradation by activated protein C (APC), thus the coag cascade remains activated for longer than normal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Manifestations of FVLM?

A
  1. VTE (3-6 fold inc risk if hetero, 30-140 fold inc risk if homo)
  2. Cerebral, mesenteric, portal vein and postsurgical thrombosis.
  3. Pregnancy loss.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Second most common inherited HS?

A

Prothrombin G202120A Mutation (affects 1-3% of pop)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Mechanism behind Prothrombin G202120A mut?

A

AD mut of prothrombin gene leading to elevated circulating plasma levels of prothrombin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Antithrombin III Function?

A

Serine protease inhibitor (syn in liver). A natural antigoag that inactivates thrombin (IIa) and FXa (and to lesser extent FIXa, FXIa, FXIIa).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Two forms of Antithrombin III Deficiency?

A

Type 1: quantitative def (low levels of anticoag)

Type 2: qualitative (normal levels of improper function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Acquired causes of Antithrombin III Def?

A
  1. Increased consumption due to:
    • Inc coag (DIC, sev injury/trauma, cardiopulm bypass, MAHA)
    • endothelial damage (hemolytic-uremic syn)
    • venoocclusive dis (in BMT recip)
  2. Decreased synthesis:
    • Chronic liver dis
  3. Protein loss:
    • Nephrotic syn
    • Ascites
    • Protein-losing enteropathy
  4. Meds
    • Heparin (-induced thrombocytopenia; pro coag effect)
    • L-asparaginase (impaired prot syn)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Function of Protein C and S?

A

Activated protein C (APC) combines with protein S on the plt surface to inactivate FVa and FVIIIa.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Acquired Protein C or S Deficiency?

A
  1. Liver disease (dec synthesis)
  2. Vit K def
  3. Warfarin use
  4. Pregnancy
  5. Sex hormone therapy
  6. Chronic inf (eg. HIV)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is Homocysteine?

A

A sulfhydryl-containing aa formed during methionine metab. High levels lead to inc risk of venous and arterial thrombosis - mech not clear, possibly related to endothelial dysfunction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mechanisms behind inherited Hyperhomocysteinemia?

A

Mut in homocysteine pathway enzymes. Commonly a C to T missense mut (sub Val for Ala) in Methyltetrahydrofolate reductase (MTFR) gene, resulting in hypofunctioning, thermolabile variant and elevated homocysteine levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Manifestations of hyperhomocysteinemia?

A
  1. Increased risk of cardiovascular events

2. 2-4 fold increased risk of VTE (20-fold if coexpressed with FVLM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Acquired causes of hyperhomocysteinemia?

A
  1. Renal or thyroid disease
  2. Smoking
  3. Aging
  4. Vit B12, B6, or folate deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What mut is Sickle Cell Disease caused by?

A

AR hemolytic anemia caused by single nucleotide mut substituting Val for Glutamic acid at 6th position of the B-hgb gene, causing polymerization of Hgb when deoxygenated and leading to Hgb S.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Mechanism behind Sickle Cell Dis?

A

Acidosis or hypoxia lead to abnormal polymerization of Hgb tetramers and formation of sickled erythrocytes that are less flexible, prone to hemolysis and adherent to the endothelium.

18
Q

Problem with Sickled cells and their manifestation?

A

Erythrocytes become lodged within smaller vessels causing vascular obstruction, ischemia, and tissue necrosis.

19
Q

What are the acquired hypercoagulable states?

A
  1. Warfarin-induced skin necrosis (WISN)
  2. Heparin-induced thrombocytopenia
  3. Antiphospholipid syndrome
  4. Thrombotic thrombocytopenic purpura
  5. Cryoglobulinemia
  6. Cryofibrinogenemia
  7. Immobilization
  8. Obesity
  9. Cancer
  10. Pregnancy
  11. Meds
20
Q

MOA of Warfarin?

A

Inhibits synthesis of vit K dependent clotting factors: FII, FVII, FIX and FX, and proteins C and S.

21
Q

WISN affects what % of warfarin users?

22
Q

Mechanisms behind WISN?

A

Due to distinct half-lives of mediating factors. Prot C has a shorter half-life (6-8hrs) than other clotting factors and is depleted earliest within the first few days of therapy before FX and FII disappear (half lives 2-5days), resulting in a relative hypercoagulability during the initial 24-72hrs of warfarin therapy.

23
Q

Risk factors for WISN?

A
  1. Protein C, S, FVL, and ATIII deficiencies
  2. HIT
  3. Malignancy
24
Q

Why might you not be able to see WISN on bloodwork?

A

PT/INR (used to eval efficacy of warfarin) is highly dependent on FVII which also has a short half-life (4-6hrs) therefore allowing misleading therapeutic INR measurements during the hypercoagulable window.

25
Frequency of HIT?
1-5% of pts on Heparin; differs between specific Heparin agents.
26
Types of HIT?
Type 1: Non-immune mediated transitory, mild, and asymp reduction in plts 1-2d into thx. Type 2: Heparin dependent IgG Abs bound to plt Fc gamma IIa receptors w/in the Heparin/plt factor 4 complex, leading to plt activation and clotting. Incurs a >50% decrease in plts from baseline w/ thrombosis occuring 5-14d after initiating thx.
27
Mechanisms behind thrombosis in Antiphospholipid syndrom?
Acquired Abs against various phospholipid-binding proteins (lupus anticoagulant, anti-cardiolipin Ab, and anti-beta-2-glycoprotein-1 Ab). Suggested mech of thrombosis include: - Complement activation - Plt activation (via p38MAPK/cPLA2) - Activation of endothelial cells/Monocytes (via Toll-like receptor-4, annexin A2, and heparin sulfate moiety of the cell mem) - Upregulation of Tissue Factor (TF) and proinflammatory cytokines (via nuclear factor-kB)
28
How is the coagulation cascade started in the extrinsic pathway (major pathway)?
Exposure of Tissue Factor (TF) on damaged endothelial cells to circulating FVII leads to autoactivated FVIIa. The FVIIa-TF complex cleaves FX into FXa, which associates with FV to form prothrombinase, which converts Prothrombin (FII) to Thrombin (FIIa). Thrombin then cleaves Fibrinogen to form Fibrin, thereby initiating the clot.
29
How is the Intrinsic pathway initiated?
Triggered by activation of the contact system, involving FXII, FXI, plasma kallikrein (PK) and high molecular weight kininogen (HMWK). FXII and HMWK make contact w/ negative charges underlying the injured endothelium, which activates FXI to FXIa, which then activates FIX to FIXa, which with its cofactor FVIII, activates FX to FXa...
30
What are the 3 endogenous mechanisms to keep coagulation in check?
1. Thrombin changes into an anticoagulant factor upon binding w/ thrombomodulin (TM - an endothelium bound glycoprotein). This complex loses the ability to clot Fibrinogen. 1a. The thrombin-TM complex allows rapid cleavage and production of activated protein C (APC), which with its cofactor protein S (on endo or plt surface), proteolytically inactivates FV and FVIII (further downreg thrombin formation) 2. Circulating protease inhibitors (tissue factor pathway inhibitor (TFPI), C1 inhibitor, antithrombin III (ATIII)), inactivate coagulation factors to prevent expansion of clotting adjacent to damaged tissue. 3. Thrombin dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI), hinders fibrinolysis inside the clot.
31
What does von Willebrand factor (vWF) do?
Present on exposed subendothelial connective tissue, vWF multimers bind plts to the injured site.
32
What is ADAMTS13?
A plasma protease that cleaves vWF multimers w/in growing plt aggregates to limit thrombus formation.
33
Mechanism behind TTP?
Problem with ADAMTS13 leading to plt rich microvascular thrombosis.
34
Inherited and acquired causes of TTP?
1. Inherited TTP due to absent or sev reduced plasma ADAMTS13 activity (multiple dif muts, hetero or homo). 2. Acquired TTP is caused by IgG autoantibodies targetting ADAMTS13. Meds include Ticlopidine or Clopidogrel. Note HLA-DRB1*11 is a risk factor for acq TTP.
35
What is Cryoglobulinemia?
The presence of single or mixed immunoglobulins that alter in confirmation and precipitate in the serum at temps below 37*C. Cryoprecipitate results from reduced solubility of IgM-IgG immune complex, which deposits on small vessel walls and activates the complement cascade > plugging/thrombosis. C3a and C5a may act as chemotactic agents of inflam leading to vasculitis.
36
What are the three types of cryoglobulinemia?
Type I (10-15%): single monoclonal immunoglobulins, usually IgM, associated with lymphoproliferative d/o (Waldenstrom macroglobulinemia, MM) Type II (50-60%): immune complexes of polyclonal IgGs w/ rheaumatoid factor activity. Type III (30-40%): monoclonal or polyclonal IgM also w/ RF activity. * Both II and III are assoc w/ infections (esp HCV), autoimmunity, and neoplasm.
37
What is Cryofibrinogemia?
A rare disorder caused by cryoprotein of fibrin, fibrinogen, and fibrin split products w/ albumin, plasma prots and Ig's, that precipitates in plasma on cooling to 4*C (redissolves w/ warming to 37*C). Leads to thrombotic occlusion of small and medium arteries. Usually associated with inflammatory d/o, infection or malignancy.
38
Factors that increase immobilization?
1. Bed rest 2. Long travel 3. Fractures 4. Plaster casts 5. Neuromuscular impairment 6. Surgery
39
Thrombosis risk in obesity?
Imparts a 2-3 fold increased risk of VTE in both sexes. Abdominal obesity a stronger risk factor then BMI.
40
Thrombosis risk in pregnancy?
Imparts a 3-4 fold increased risk of arterial thromboembolism, 4-5 fold increased risk of VTE (20-fold postpartum). Note VTE 4x more freq then arterial thrombosis, w/ 80% being DVTs (20% PEs).
41
Mechanisms behind increased risk of thrombosis in pregnancy?
1. Hypercoagulability (inc FVII, FVIII, FX, vWF, and fibrinogen, and dec Protein S) 2. Hormone-induced decreased capacitance and outflow. 3. Mechanical obstruction from uterus 4. Decreased mobility.
42
Medications associated with hypercoagulability?
1. Warfarin 2. Heparin 3. OCP 4. 5-fluorouracil 5. Thalidomide analogs 6. Antiangiogenic agents 7. Epidermal growth factor rec inh. Also: antipsychotics, chemotherapeutic agens, cocaine, contrast media, Cox-2 inh, ephedra, erythropoietin, GCSF, heparin, OCP/HRT, immunosupressants (cyclosporine, glucocorticosteroids, sirolimus, interferon alpha, IVIG), metformin, quinine, rFVIIa, SSRIs, Sildenafil, tissue plasminogen activator (tPA), tranexamic acid.

JAAD CME (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions