Coagulation

normal circulation

normal circulation requires free blood flow through vessels.
•Clotting prevents excessive blood loss after vessel injury.
•Blood contains cells and mediators that maintain a balance
between coagulation and anticoagulation.

Coagulation

→ Triggered by tissue damage or endothelial injury and platelet
activation
→ Involves intrinsic and extrinsic pathways
→ Results in fibrin clot formation

anticoagulation

→ Prevents excessive clot formation
→ Includes heparin and other endogenous inhibitors
→ Maintains blood flow in healthy vessels

coag and anticoag balance

Coagulation: prevents blood loss after injury
→ Anticoagulation: prevents thrombosis and vessel blockage

nrormal hemostasis - balance

→ Injury → clot formation (hemostasis)
→ Healing → clot breakdown (fibrinolysis)

increased coagulation = 

• thrombosis and embolism

• ↓ Perfusion → ischemia or infarction
  → Tx: Anticoagulants (Heparin, Warfarin, DOACs, Antiplatelets)

decreased coagulation =

• bleeding disorders

• ↓ Clot formation → prolonged bleeding
  → Tx: Replace missing factors or use hemostatics
  → e.g., Factor VIII or IX, Cryoprecipitate, Desmopressin

what balance fails - goals

maintain vascular integrity - prevent both bleeding and unwanted clotting

Coagulation related factors

• thrombogenic factors - promote clot formation and hemostasis

• vitamin k, calcium, von willebrand

Antithrombogenic factors 

• inhibit clot formation or promote clot breakdown

• Protein c and s, nitric oxide, plasminogen, tPA

Common labs - 1

PT / INR → Extrinsic + common pathways; monitors warfarin
2. aPTT → Intrinsic + common pathways; monitors heparin
3. Anti-Xa (Xa Test) → Measures Factor Xa inhibition

Common labs - 2

1. Platelet Count → Number of platelets; screens for bleeding or clotting risk

2. Platelet Function Analyzer (PFA-100) → Replaces bleeding time; assesses platelet function

Common labs - 3

• liver function / clotting factor production 

• LFTs → Evaluate liver enzymes and protein synthesis; liver makes most clotting factors

D-dimer test - purpose

Detects fibrin degradation products → indicates recent or ongoing clot formation and breakdown

D-dimer test - use

Screening for thrombotic disorders → DVT, PE, DIC
•Often used to rule out (not confirm) thrombosis when low clinical suspicion

how to interpret D-dimer test

↑ D-dimer → clot presence or breakdown (many possible causes)
•Normal D-dimer → helps rule out DVT/PE

coagulation disorders - thrombotic disorders causes and results in..

Cause: ↑ Coagulation or ↓ natural anticoagulants
→ Inherited: Factor V Leiden, Prothrombin G20210A, Deficiencies
→ Acquired: Immobility, cancer, pregnancy, estrogen, surgery, inflammation
→ Results: VTE, DVT, PE, CVA, PAD, MI

coagulation disorders - bleeding disorder causes and results

Cause: ↓ Coagulation factors or platelet dysfunction
→ Inherited: Hemophilia A/B, von Willebrand Disease
→ Acquired: ITP, DIC
→ Results: Prolonged bleeding, petechiae, bruising, hemorrhage

Major clotting disorders - def

→ Conditions where the blood clots too easily → risk for DVT, PE, stroke, MI, or pregnancy loss

Major clotting disorders - most common inherited type

• Factor v Leiden - most common - 5% of caucasians 

• Prothrombin

• Protein C / S deficiency

• antiphospholipid syndrome (APS)

Major clotting disorders - sign

• Leg swelling/pain, redness, chest pain, SOB, recurrent miscarriage

Factor V Leiden - def

Inherited point mutation in the F5 gene causing Factor V resistance to Protein C inactivation

Factor V Leiden - MOA

Normally, Activated Protein C (APC) inactivates Factor V to slow clotting
→ Mutation → Factor V stays active → ↑ thrombin generation → hypercoagulability

Factor V leiden — Clinical effects

↑ risk of DVT, PE, and pregnancy loss
→ Usually venous,

Factor Diagnosis -

APC resistance assay or genetic test for F5 mutation

Clotting disorders: causes and management

→ Inherited clotting disorders ↓ common than inherited bleeding disorders
→ Acquired hypercoagulable states ↑ common than inherited
clotting disorders → main cause of adult thrombosis

Acquired causes - clotting

Immobility or surgery
→ Malignancy (cancer-associated clots)
→ Pregnancy or hormone therapy (↑ estrogen)
→ Obesity, age, smoking

Clotting disorders: Pathophysiology and tx

• Imbalance of coagulation → ↑ thrombin → ↑ fibrin → pathologic clots
  General Treatment:
  → Anticoagulants (Heparin, LMWH, Warfarin, DOACs)
  → Lifestyle: mobility, stop smoking, avoid estrogen therapy

overview of antithrombotic agents

• anticoagulants - inhibit clotting factors

• antiplatelets - inhibit platelet activation

• throbolytics - dissolve clots 

anticoagulants - purpose

Prevent and treat venous or cardiac thromboembolism (e.g., DVT, PE, Afib, mechanical valves)

anticoagulants = mechanism

Interfere with clotting factors in the coagulation cascade → ↓ fibrin formation

anticoagulants - examples

1. Heparin - enhance antithrombin and inhibits thrombin and Xa

2. Warfarin - inhibit vitamin K - dependent factors

3. DOACs - directly inhibit thrombin or Factor Xa

Heparin-induced thrombocytopenia (HIT) - def

Immune-mediated reaction to heparin → antibodies form against heparin–platelet factor 4 complex → Causes platelet activation → thrombosis, not bleeding

Heparin-induced thrombocytopenia (HIT) - testing and signs

testing:

CBC: ↓ platelets (≥50% drop from baseline)
→ ELISA or serotonin release assay (SRA) confirms diagnosis

signs:

New or worsening thrombosis, not bleeding
→ May see skin necrosis at injection sites, limb ischemia, DVT, or PE

Heparin-induced thrombocytopenia (HIT) - treatment

Stop all heparin immediately (including flushes)
→ Start non-heparin anticoagulant (e.g., argatroban or fondaparinux)
→ Avoid platelet transfusion unless life-threatening bleed
→ Do NOT restart heparin or LMWH

nursing considerations for anticoags

• blood for bleeding

• avoid NSAIDS/ aspirin

• hold before surgery

• use soft toothbrush

• monitors labs

• education: do not skip or double dose

• know antidotes

• report signs of bleeding and clotting

Antiplatelet therapy overview

• prevent thrombosis (CAD, stroke, PAD, ACS, post-stent)

• decreases platelet aggregation

Antiplatelet - example

aspirin - inhibits TXA2

clopidogrel - blocks ADP p2Y12 receptor

GP IIb/IIIa - abciximab

Thrombolytic therapy

• dissolve clots (MI, PE, ischemic stroke)

• can cause bleeding

• example: alteplase

bleeding disorders - types

1. von willebrand disease - inherited

2. hemophilia A and B

3. ITP - acquired

4. DIC - complication of sepsis, trauma

von willebrand disease - def and signs

• most common inherited bleeding disorder = deficiency or dysfunction of vWF

• easy bruising, nosebleeds, heavy periods

von willebrand disease - treatment

Desmopressin (DDAVP) ↑ vWF release (mild cases)
→ vWF/Factor VIII concentrate for severe cases
→ Antifibrinolytics (e.g., TXA)

Hemophilia A

• Factor 8

• X-linked genetic disorder → deficient Factor VIII → impaired intrinsic pathway

• increased aPTT

• prolonged bleding, blood in joints, brusing 

Hemophilia A - treatment

Factor VIII replacement (on-demand or prophylaxis)
→ Desmopressin (DDAVP) for mild cases
→ Avoid NSAIDs / trauma

Hemophilia B

• factor 9

• X-linked Factor IX deficiency

• increased aPTT

• prolonged bleeding, joint pain and swelling

Hemophilia B - treatment

Factor IX replacement (on-demand or prophylaxis)
→ Antifibrinolytics (e.g., TXA) to stabilize clots

Disseminated intravascular coagulation (DIC) - def

Secondary process → widespread activation of clotting → microthrombi + factor consumption → bleeding

• increased PT and aPTT, d-dimer, decreased platelets and fibrinogen

Disseminated intravascular coagulation (DIC) - signs and treatment

• bleeding, thrombosis, organ ischemia, shock

treatment:

• treat underlying cause (sepsis, trauma)

• FFP, platelets

• heparin if mostly thrombotic 

Immune Thrombocytopenic Purpura (ITP) - def and signs

Autoimmune platelet destruction → isolated thrombocytopenia (plt < 100 K)

• low platelets, normal WBC

• petechiae, and purpura, mucosal bleeding, nosebleeds

Immune Thrombocytopenic Purpura (ITP) - treatment

• first-line - corticosteroids

• no NSAIDS or aspirin

liver disease on coagulation

Coagulopathy due to impaired synthesis of clotting factors
→ ↑ Risk for DIC
→ Treatment: Based on coagulation study results

hypothermia and metabolic acidosis

→ ↓ Coagulation capacity
→ Causes: platelet dysfunction, ↓ factor synthesis, ↓ inhibitor activity
→ Treatment: Rewarming and correction of acidosis

hemostatic therapy

Purpose: Opposite of anticoagulants → Prevent fibrin breakdown → enhance clot stability
•Indications: Surgical bleeding, trauma, menorrhagia, hemophilia

not for: DIC

balance

increased coagulation - treat with anticoagulants or antiplatelets

decreased coagulation - treat with hemostatics / factor replacement

goal: maintain vascular integrity and safe circulation