Coagulation Disorders & Modifiers

Hemostasis stages

1. Vasoconstriction

2. Platelet plug

3. Coagulation

Primary hemostasis

Forms a platelet plug

Secondary hemostasis

Produces fibrin to stabilize the clot

Extrinsic pathway

Tissue-factor-initiated pathway

Intrinsic pathway

Amplifies coagulation by making making more Factor 10 and thrombin

Common pathway

Converts prothrombin to thrombin and fibrinogen to fibrin

Clot stabilization

Factor XIII cross-links fibrin strands

Hemostasis

Process that stops bleeding

Platelet adhesion

Platelets attaching to an injured vessel

Platelet aggregation

Platelets binding to one another

Coagulation cascade

Sequence of clotting-factor activation

Thrombin (factor IIa)

Converts fibrinogen to fibrin

Fibrin

Protein strands that stabilize a clot

Fibrinolysis

Breakdown of fibrin clot

Plasmin

Enzyme that breaks down fibrin

Hypercoagulability

Increased tendency to form clots

Thrombosis

Formation of clot within blood vessel

Thromboembolism

Clot that travels and obstructs a blood vessel

DVT

Clot in a deep vein

PE

Clot obstructing pulmonary circulation

Venous stasis

Slowed venous blood flow

Thrombophilia

Predisposition to thrmbosis

Factor V Leiden

Inherited resistance to activated protein C

Antiphospjolipid syndrome

Autoimmune disorder linked to thrmbosis and pregnancy loss

von Willebrand factor

Supports platelet adhesion

HIT

Immune platelet activation after heparin exposure

Hemarthrosis

Bleeding into a joint

Disseminated intravascular coagulation

Widespread clotting with consumption and bleeding

Immune thrombocytopenia

Autoimmune destruction of platelets

PT / INR

Tests extrinsic/common pathways; monitors warfarin

aPTT

Tests intrinsic/common pathways; monitors IV heparin

Anti-Xa

Assay used to monitor selected heparin therapy

D-dimer

MArker of fibrin breakdown

Fibrinogen

Platelet converted to fibrin

Hemostatic agent

Drug that promotes or stabilizes clot formation

Prothrombin complex concentrate

Concentrated clotting factors used for selected reversals

Reversal agent

Treatment used to counter an anticoagulant effect

Platelet count

Identifies thrombocytopenia and bleeding risk

LFTs

Liver produces most clotting factors

Hypercoagulability

Increase thrombin → increase fibrin → pathologic clot formation

Vascular obstruction

Decrease perfusion → ischemia or infarction

S/S DVT

Unilateral leg swelling, pain, warmth, redness

S/S PE

Sudden dyspnea, chest pain, tachycardia

Antithrombotic therapy

• Purpose: Prevent or treat harmful blood clot formation (DVT, PE, stroke, ACS).

• Mechanism: Reduce platelet aggregation, inhibit clotting factors, or dissolve fibrin clots.

• Major Drug Classes & Examples:

1. Antiplatelets – aspirin (↓ TXA₂); clopidogrel (blocks P2Y₁₂), eptifibatide(

GPIIb/IIIa)

2. Anticoagulants – heparin/LMWH (↑ antithrombin); warfarin (↓ vitamin K

factors); DOACs (inhibit IIa or Xa).

3. Thrombolytics – alteplase, tenecteplase (activate plasmin to break down fibrin).

• Major Risk: Bleeding, including intracranial hemorrhage with thrombolytics.

• Clinical Pearl:

• Anticoagulants prevent clot growth

• Thrombolytics dissolve existing clots

Aspirin

• COX-1 Inhibitor

MOA: Irreversibly inhibits COX-1 → ↓ Thromboxane A₂ → ↓ Platelets activation and aggregation

• Route: PO

• Major ADR: Bleeding, GI irritation/ulcers

• Safety: Avoid with active bleeding; Reye syndrome risk in children with viral illnesses

Nursing Priorities

• Monitor: Bleeding, bruising, black/tarry stools

• Interactions: NSAIDs/anticoagulants → ↑ Bleeding risk

• Teaching: Do not stop prescribed therapy without provider instructions

• Clinical Pearl: Antiplatelets prevent platelet aggregation → Help prevent

arterial clots.

Clopidogrel

• P2Y12 Receptor Inhibitors

• MOA: Blocks P2Y₁₂ receptors → ↓ Platelet activation and aggregation

• Route: PO

• Major ADR: Bleeding/hemorrhage

• Black Box Warning: Reduced effectiveness in CYP2C19 poor metabolizers

• Nursing Priorities:

• Monitor: Bleeding, bruising, black/tarry stools

• Interactions: NSAIDs/anticoagulants → ↑ Bleeding risk

• Teaching: Do not stop prescribed therapy without provider instructions

• Clinical Pearl: Antiplatelets prevent platelet aggregation → Help prevent arterial clots.

Eptifibatide

• MOA: Blocks GP IIb/IIIa receptors → Prevents fibrinogen binding → ↓ Platelet aggregation

• Route: IV

• Clinical Use: ACS and other selected coronary interventions

• Major ADR: Severe bleeding, thrombocytopenia

• Nursing Priorities

• Monitor: Bleeding, platelet count, hemoglobin/hematocrit

• Assess: IV/access sites → Bleeding or hematoma

• Renal Function: ↓ Kidney function → May require dose adjustment

• Interactions: Anticoagulants/other antiplatelets → ↑ Bleeding risk

• Safety: Avoid unnecessary invasive procedures; report significant bleeding

• Clinical Pearl: GP IIb/IIIa inhibitors block the final common step of platelet aggregation.

Heparin

• UNfractionated Heparin

MOA: Inhibits Factor Xa and thrombin (IIa)

• Route: IV or SC → Rapid anticoagulation

• Major ADR: Bleeding, heparin-induced thrombocytopenia (HIT)

• Monitoring: aPTT or anti-Xa, platelets

• Antidote: Protamine sulfate

• Nursing Safety

• Both: Monitor bleeding; avoid IM injections

• Black Box: Spinal/epidural bleeding → Possible paralysis

• Clinical Pearl:

• UFH = aPTT/anti-Xa monitoring

• LMWH = No routine aPTT monitoring.

Enoxaparin

• MOA: Mainly inhibits Factor Xa

• Route: SC → Rotate abdominal injection sites; do not rub

• Major ADR: Bleeding; HIT less common

• Monitoring: No routine aPTT; monitor platelets and renal function

• Reversal: Protamine sulfate → Partial reversal

• Nursing Safety

• Both: Monitor bleeding; avoid IM injections

• Black Box: Spinal/epidural bleeding → Possible paralysis

• Clinical Pearl:

• UFH = aPTT/anti-Xa monitoring

• LMWH = No routine aPTT monitoring.

Hypercoagulability inherited causes

Factor V Leiden, prothrombin gene mutation, and deficiencies of protein C/S or antithrombin

Hypercoagulability acquired contributors

Antiphospholipid syndrome, malignancy, estrogen exposure, pregnancy/postpartum, surgery/trauma

HIT

• Definition: Serious immune reaction to heparin → ↑ Platelet activation → ↑ Blood clots (thrombosis)

• Pathophysiology: Antibodies form against heparin–PF4 complexes → Platelets become activated and consumed → ↓ Platelet count

• Key Finding: ≥50% drop in platelets from baseline → Usually occurs 5–10 days after starting heparin

• Signs & Symptoms: New DVT/PE, limb pain/ischemia, or skin necrosis → Indicates possible thrombosis

• Nursing Priorities

• Monitor: Platelet trends → ≥50% decrease or new thrombosis → Suspect HIT

• Take Action: Suspected HIT → Stop ALL heparin (including flushes) → Notify provider immediately

• Treatment: Stop heparin → And start alternative non-heparin anticoagulant (e.g., argatroban, bivaliriudin – IV direct thrombin inhibitors)

• Safety: Avoid LMWH and routine platelet transfusions in acute HIT

• Clinical Pearl: HIT = ↓ Platelets but ↑ Risk of Blood Clots — NOT primarily bleeding.

Warfarin

• Vitamin K antagonist

MOA: Blocks vitamin K recycling → ↓ Production of clotting factors II, VII,

IX, X

• Route: PO → Delayed anticoagulant effect

• Major ADR: Bleeding/hemorrhage

• Black Box: Major or fatal bleeding

• Contraindications: Active major bleeding; generally avoided in pregnancy

• Interactions: Many medications and changes in vitamin K intake affect INR

• Nursing Priorities

• Monitor: PT/INR → Usually 2–3; some mechanical valves require higher targets

• Diet: Maintain consistent vitamin K intake (leafy greens)

• Antidote: Vitamin K (phytonadione)

• Severe Bleeding: 4-factor Prothrombin Complex Concentrate (PCC) + IV vitamin K

• Teaching: Regular INR checks; report bleeding

• Clinical Pearls

• Warfarin = INR monitoring + Vitamin K reversal.

• Warfarin is used for mechanical heart valves; DOACs are not.

Apixaban

• DOACs

Factor Xa Inhibitors

MOA: Blocks Factor Xa → ↓ Thrombin formation

• Route: PO → Usually twice daily

• Major ADR: Bleeding/hemorrhage

• Reversal: 4-factor PCC may be used for severe bleeding per protocol

• Nursing Priorities

• Monitoring: No routine INR or aPTT; assess bleeding, CBC, kidney function

• Interactions: NSAIDs/aspirin → ↑ Bleeding risk

• Black Box: Stopping early → ↑ Thrombosis; Spinal/epidural bleeding risk

• Teaching: Do not stop abruptly; take consistently

• Clinical Pearl: apixaban blocks Factor Xa; dabigatran blocks thrombin.

Dabigatran

• DOACs

Direct Thrombin (IIa) inhibitors

MOA: Blocks thrombin (IIa) → ↓ Fibrin formation

• Route: PO → Usually twice daily

• Major ADR: Bleeding/hemorrhage

• Reversal: Idarucizumab (Praxbind) → Specific antidote

• Nursing Priorities

• Monitoring: No routine INR or aPTT; assess bleeding, CBC, kidney function

• Interactions: NSAIDs/aspirin → ↑ Bleeding risk

• Black Box: Stopping early → ↑ Thrombosis; Spinal/epidural bleeding risk

• Teaching: Do not stop abruptly; take consistently

• Clinical Pearl: apixaban blocks Factor Xa; dabigatran blocks thrombin.

Nursing considerations Anticoagulants

1. Assess for bleeding → Bruising, bleeding gums, hematuria, black/tarry stools

2. Monitor for thrombosis → Leg swelling/pain, sudden dyspnea, chest pain

3. Avoid NSAIDs/aspirin unless prescribed → ↑ Bleeding risk

4. Bleeding precautions → Soft toothbrush, electric razor, prevent falls/injury

5. Before procedures → Notify provider; anticoagulants may need to be held as ordered

6. Patient education → Take exactly as prescribed; never skip, double, or stop doses without instructions

7. Report immediately → Uncontrolled bleeding or symptoms of DVT/PE

• Clinical Pearl: Anticoagulants prevent clot formation but increase bleeding risk.

Alteplase

• Thrombolytics (Fibrinolytics)

Similar Drug: Tenecteplase (TNKase)

• MOA: Converts plasminogen → plasmin → Breaks down fibrin → Dissolves existing clots

• Route: IV; may be delivered directly to a clot during selected procedures

• Clinical Use: Selected patients with acute ischemic stroke, PE, or MI

• Major ADR: Severe bleeding, especially intracranial hemorrhage

• Contraindications: Active bleeding, intracranial hemorrhage, or other major bleeding risks

• Nursing Priorities

• Before Administration: Screen for contraindications; verify treatment eligibility and timing

• Monitor: Neurological status, vital signs, bleeding

• Safety: Avoid unnecessary injections/invasive procedures

• Report Immediately: Severe headache, sudden neurological changes, or bleeding

• Clinical Pearl: Anticoagulants prevent clot growth; thrombolytics dissolve existing clots

Von Willebrand Disease (vWD)

• Definition: → Most common inherited bleeding disorder →

deficiency or dysfunction of vWF (platelet adhesion defect) → vWD Types: Type 1 – ↓ vWF quantity (mild, most common);

Type 2 – ↓ vWF function; Type 3 – Nearly absent vWF (severe, rare).

• Testing: → ↓ vWF antigen/activity, ± ↓ Factor VIII

• S/S: → Easy bruising, nosebleeds, heavy menses, ↑ bleeding after

surgery, dental work, or injury

• Treatment:

• Depends on type and severity → Desmopressin (DDAVP) ↑ vWF release (mild cases) → vWF/Factor VIII concentrate for severe cases → Antifibrinolytics (e.g., TXA)

Hemophilia A & B

Definition:

• X-linked bleeding disorders affecting the intrinsic pathway

• Hemophilia A: Factor VIII deficiency

• Hemophilia B: Factor IX deficiency

• Testing:

• ↑ aPTT (normal PT and platelets)

• Factor VIII or IX assay → Differentiates A vs. B

• Signs & Symptoms:

• Prolonged bleeding, easy bruising

• Hemarthrosis → Joint pain and swelling

• Excessive bleeding after injury or surgery

• Treatment:

• Factor VIII replacement → Hemophilia A

• Factor IX replacement → Hemophilia B

• DDAVP → Mild Hemophilia A

• Antifibrinolytics (TXA) → Stabilize clots

• Avoid NSAIDs and trauma

Disseminated INtravascular Coagulation (DIC)

• Definition:

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

• Testing: → ↑ PT / aPTT, ↑ D-dimer, ↓ platelets, ↓ fibrinogen, fragmented

RBCs (schistocytes) by mechanical damage

• S/S: → Bleeding (bruising, oozing), thrombosis, organ ischemia, shock

• Treatment: → Treat underlying cause (sepsis, trauma, obstetric) → Supportive: Fresh frozen platelets (FFP) , platelets, cryoprecipitate if bleeding → Heparin if predominantly thrombotic

• Clinical Pearl: DIC causes both clotting and bleeding because microthrombi consume platelets and clotting factors. Treat the underlying cause first!

Immune Thrombocytopenic Purpura (ITP)

• Definition:

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

• Testing: → CBC = low platelets, normal WBC/RBC; peripheral smear normal morphology

• S/S: → Petechiae, purpura, mucosal bleeding, nosebleeds, gum bleeding

• Treatment: → Corticosteroids (first line) → IVIG or Rho(D) immune globulin if severe → Splenectomy for refractory cases → Avoid NSAIDs / aspirin

Hemostatic Therapy Overview

• Purpose: Prevent or control excessive bleeding caused by impaired clot formation or excessive clot breakdown

• Mechanism: Promote hemostasis through two major actions:

1. ↑ Clotting factor availability → Improved clot formation

2. ↓ Fibrinolysis → Stabilization of existing clots

• Examples:

• Desmopressin (DDAVP) – ↑ Release of vWF and Factor VIII → Improves clot formation

• Tranexamic Acid (TXA) –Blocks plasminogen binding to fibrin → prevents clot breakdown.

• Aminocaproic Acid (Amicar) –Blocks plasminogen activation → prevents clot

breakdown.

• Major Risks: thromboembolic complications in susceptible patients

• Clinical Pearl:

• DDAVP promotes clot formation

• Antifibrinolytics prevent clot breakdown.

Desmopressin

Hemostatic Agent

• Class: Synthetic ADH analog → Hemostatic agent

• MOA: Stimulates V₂ receptors → ↑ Release of vWF and Factor VIII → ↑ Clot formation

• Route: IV, SC, intranasal (formulation-dependent)

• Clinical Use: Selected patients with mild hemophilia A or von Willebrand disease (primarily type 1)

• Major ADR: Hyponatremia, water intoxication, headache, flushing

• Contraindications: Hyponatremia, significant renal impairment, certain

cardiac conditions

• Nursing Priorities

• Monitor: Serum sodium, fluid balance, urine output

• Fluid Restriction: Limit free water → Prevent water intoxication

• Assess: Headache, confusion, weight gain → Possible hyponatremia

• Safety: Monitor response to therapy; repeated doses may have ↓ effect over time (tachyphylaxis)

• Clinical Pearl:

• DDAVP increases vWF and Factor VIII

• Antifibrinolytics prevent fibrin breakdown

TXA

• Antifibrinolytic

MOA: Blocks plasminogen binding to fibrin → ↓ Fibrin breakdown

• Route: PO, IV, topical (often off-label)

• Uses: Trauma, surgery, postpartum hemorrhage, heavy menses,

epistaxis

• Major ADR: Seizures (high doses), hypotension (rapid IV), thrombotic

complications

• Nursing Priorities

• Monitor: Bleeding control and signs of DVT/PE

• Administration: Give IV slowly → Rapid administration may cause hypotension

• Renal Function: Assess kidney function → May require dose adjustment

• Safety: Avoid with active intravascular clotting; assess thrombotic risk

• Clinical Pearl:

• Both drugs prevent fibrin breakdown → Stabilize existing clots.

Aminocaproic Acid

• MOA: Inhibits plasminogen activation → ↓ Plasmin → ↓ Fibrin breakdown

• Route: PO/IV

• Uses: Surgical bleeding, excessive fibrinolysis, hemophilia-related bleeding

• Major ADR: Hypotension (rapid IV), myopathy, thrombotic complications

• Nursing Priorities

• Monitor: Bleeding control and signs of DVT/PE

• Administration: Give IV slowly → Rapid administration may cause hypotension

• Renal Function: Assess kidney function → May require dose adjustment

• Safety: Avoid with active intravascular clotting; assess thrombotic risk

• Clinical Pearl:

• Both drugs prevent fibrin breakdown → Stabilize existing clots.