10.4 Coagulopathies: Heparin-Induced Thrombocytopenia, DIC and Bleeding Disorders

Heparin-Induced Thrombocytopenia: the Highest-Yield Coagulopathy in Cardiac Care

Nearly every patient in a cardiac unit is exposed to heparin — therapeutic infusions for ACS, prophylactic subcutaneous doses, line flushes, heparin-bonded pulmonary artery catheters and intra-aortic balloon pumps, cardiopulmonary bypass, and dialysis circuits. Heparin-induced thrombocytopenia (HIT) is therefore a CMC exam staple.

Distinguish the two types immediately. Type 1 is a non-immune, direct platelet-aggregating effect: a mild fall within the first 1 to 2 days, a nadir rarely below 100 x 10^9/L, spontaneous recovery even with continued heparin, and no thrombotic risk. Type 2 is the immune, prothrombotic syndrome that everything below describes.

Pathophysiology and timing

Heparin binds platelet factor 4 (PF4), a positively charged protein released from platelet alpha granules. The heparin-PF4 complex is immunogenic; IgG antibodies form against it, and the resulting immune complexes cross-link FcgammaRIIa receptors on platelets, activating them. Activated platelets aggregate, are cleared by the spleen (hence the thrombocytopenia), and shed procoagulant microparticles. The antibodies also activate monocytes and endothelium, driving tissue factor expression and explosive thrombin generation. HIT is a hypercoagulable state that happens to lower the platelet count — that paradox is the whole clinical point.

Incidence is roughly 0.2 to 5 percent, higher with unfractionated than low-molecular-weight heparin, higher in surgical than medical patients, and highest after cardiac surgery, where up to half of patients develop antibodies but only 1 to 3 percent develop clinical HIT.

The timing rules:

• Typical onset: platelet count falls by more than 50 percent from baseline on days 5 to 10 of heparin exposure. The nadir is usually 50 to 70 x 10^9/L; a count below 20 x 10^9/L argues against HIT.
• Rapid onset: the fall occurs within 24 hours of re-exposure in a patient who received heparin within the preceding 100 days and still has circulating antibodies.
• Delayed-onset HIT: thrombocytopenia and thrombosis begin days to weeks after heparin has already been stopped, sometimes after discharge.
• Note the cardiac-surgery confounder: platelets normally fall after cardiopulmonary bypass and recover by postoperative day 3 to 4. A secondary fall after day 5, or a failure to recover, is the suspicious pattern.

The 4Ts score

Interpretation: 0 to 3 = low probability (negative predictive value near 99 percent), 4 to 5 = intermediate, 6 to 8 = high probability. A low 4Ts score essentially excludes HIT and should stop the workup — testing low-probability patients generates false positives that lead to unnecessary and expensive alternative anticoagulation.

Testing

The PF4 immunoassay (ELISA) is sensitive (above 95 percent) but poorly specific; many patients have antibodies without clinical disease. The magnitude matters — an optical density above 2.0 substantially raises the likelihood of true HIT. The confirmatory functional test is the serotonin release assay (SRA), the gold standard, with high specificity but a send-out turnaround of days. You do not wait for it: treat on clinical probability and adjust.

Management rules

1. Stop ALL heparin. That means the infusion, subcutaneous prophylaxis, line flushes, heparin-bonded catheters and intra-aortic balloon pump sheaths, heparin in the dialysis or CRRT circuit, and heparin-containing total parenteral nutrition. Flag the chart and the wristband. Missing the flushes is a recurring exam trap and a real-world one.
2. Start a therapeutic-dose non-heparin anticoagulant immediately, even with isolated HIT and no clot. Untreated HIT carries a 5 to 10 percent per day risk of new thrombosis and a 30 to 50 percent overall thrombosis rate. "Stop the heparin and watch the platelets" is wrong.
   • Argatroban — direct thrombin inhibitor, hepatically cleared, half-life 40 to 50 minutes. Start at 2 mcg/kg/min, but reduce to 0.5 to 1.2 mcg/kg/min in hepatic dysfunction, heart failure, anasarca, post-cardiac-surgery and multi-organ failure. Titrate to an aPTT 1.5 to 3 times baseline and generally not above 100 seconds. It artificially prolongs the INR, which complicates warfarin transition.
   • Bivalirudin — direct thrombin inhibitor, largely enzymatic clearance with about 20 percent renal, half-life 25 minutes; the usual choice when a HIT patient needs PCI or cardiac surgery.
   • Fondaparinux — indirect factor Xa inhibitor, once-daily subcutaneous, renally cleared; avoid with creatinine clearance below 30 mL/min.
   • Direct oral anticoagulants (rivaroxaban, apixaban) are acceptable for clinically stable patients per current hematology guidance.
3. Do not give prophylactic platelet transfusions. Adding platelets to a prothrombotic state has been associated with arterial thrombosis and death. Reserve transfusion for active clinically significant bleeding.
4. Do not start or continue warfarin until the platelet count has recovered to 150 x 10^9/L or above and the patient is therapeutically anticoagulated on a non-heparin agent. Warfarin depletes protein C faster than the vitamin K-dependent procoagulant factors, and in the thrombin-saturated state of HIT this precipitates venous limb gangrene and warfarin-induced skin necrosis. If warfarin was already given, reverse it with vitamin K 5 to 10 mg IV.
5. Overlap warfarin with the parenteral agent for at least 5 days and until the INR is therapeutic. With argatroban, use a chromogenic factor X level or repeat the INR 2 hours after stopping the infusion.
6. Duration: 3 months with thrombosis; at least 4 weeks (through platelet recovery) with isolated HIT.

Nursing surveillance: trend the platelet count at least every other day in any patient receiving heparin for more than 4 days, compare against the admission baseline rather than the previous day, assess limbs for new pain, pallor, pulselessness or discoloration, watch injection sites for necrotic lesions, and educate the patient that heparin avoidance is lifelong and must be reported at every future admission.

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is systemic activation of coagulation with microvascular fibrin deposition, consumption of platelets and clotting factors, and secondary fibrinolysis. It is always a complication of something else, and the triggers relevant to cardiac care are sepsis and septic shock, prolonged cardiac arrest with ischemia-reperfusion injury, massive transfusion and trauma, extracorporeal membrane oxygenation and ventricular assist device circuits, malignancy, acute promyelocytic leukemia, hemolytic transfusion reaction, and obstetric catastrophe.

Two phenotypes matter clinically: a thrombotic (organ-failure) phenotype typical of sepsis, with microvascular thrombosis, acral ischemia, and purpura fulminans; and a fibrinolytic (bleeding) phenotype typical of acute promyelocytic leukemia, trauma, and aortic aneurysm.

The laboratory pattern:

• Falling platelet count — the trend is more informative than any single value
• Prolonged PT/INR, then prolonged aPTT
• Low fibrinogen, typically below 100 to 150 mg/dL. Beware: fibrinogen is an acute-phase reactant that rises in sepsis and after surgery, so a "normal" 200 mg/dL in a septic patient may represent a large relative fall.
• Markedly elevated D-dimer and fibrin degradation products
• Schistocytes on the peripheral smear, falling antithrombin, and falling protein C

The ISTH overt-DIC score operationalizes this: platelet count (above 100 = 0, below 100 = 1, below 50 = 2), D-dimer or fibrin marker (no rise = 0, moderate = 2, strong = 3), PT prolongation (under 3 seconds = 0, 3 to 6 seconds = 1, over 6 seconds = 2), and fibrinogen (above 100 mg/dL = 0, below 100 = 1). A score of 5 or more is compatible with overt DIC; repeat daily, because the trajectory carries the information.

Treatment principle — the one the exam tests: the treatment for DIC is treating the cause. Source control of sepsis, delivery of the fetus, restoring perfusion, treating the leukemia. Blood products are given for bleeding or a planned invasive procedure, not to normalize a number on a screen:

• Platelets if below 50 x 10^9/L with bleeding or before a procedure (below 10 to 20 x 10^9/L for prophylaxis in the non-bleeding patient)
• Fresh frozen plasma 15 to 20 mL/kg if the PT or aPTT exceeds 1.5 times normal with bleeding
• Cryoprecipitate or fibrinogen concentrate if fibrinogen is below 150 mg/dL with bleeding; roughly 10 units of cryoprecipitate raise fibrinogen by 50 to 100 mg/dL
• Therapeutic heparin only in the predominantly thrombotic phenotype — purpura fulminans, digital ischemia, large-vessel thrombosis
• Avoid antifibrinolytics such as tranexamic acid in classic DIC; blocking fibrinolysis in a patient depositing microvascular fibrin worsens organ failure. Hyperfibrinolytic variants are a specialist exception.

Differentials worth holding in mind: thrombotic thrombocytopenic purpura (severe thrombocytopenia and hemolysis with a normal PT and fibrinogen, ADAMTS13 activity below 10 percent), HIT (normal PT and fibrinogen, higher platelet nadir), liver disease (factor VIII is normal or high in liver failure but low in DIC, which is the classic discriminator), and HELLP syndrome.

Other Coagulopathies the Cardiac Nurse Must Recognize

Acquired von Willebrand syndrome

High shear stress unfolds von Willebrand factor and exposes it to cleavage by ADAMTS13, stripping out the high-molecular-weight multimers that mediate platelet adhesion. Two cardiac settings produce exactly this:

• Severe aortic stenosis. Combined with the gastrointestinal angiodysplasia that low pulse pressure and hypoxia promote, this is Heyde syndrome — the triad of severe aortic stenosis, acquired von Willebrand syndrome, and recurrent GI bleeding from angiodysplasia. Aortic valve replacement, surgical or transcatheter, corrects the coagulopathy and usually stops the bleeding.
• Continuous-flow left ventricular assist devices. GI bleeding is the leading cause of readmission in LVAD recipients, driven by the same multimer loss plus reduced pulsatility and angiodysplasia. Management includes reducing INR targets and holding aspirin, octreotide, endoscopic therapy, and in refractory cases increasing pulsatility.

The trap: in acquired von Willebrand syndrome the platelet count, PT, aPTT, and INR are all normal. A normal coagulation screen does not exclude a bleeding disorder. Diagnosis requires von Willebrand multimer analysis, a low von Willebrand factor collagen-binding-to-antigen ratio, or platelet function analyzer testing.

Post-cardiac-surgery and dilutional coagulopathy

After cardiopulmonary bypass, bleeding is usually multifactorial: hemodilution of factors and platelets, hypothermia (enzyme kinetics and platelet function are impaired below about 35 degrees Celsius — rewarm before concluding the patient has a factor deficiency), acidosis (pH below 7.1 markedly impairs thrombin generation), bypass-induced platelet dysfunction, residual or rebound heparin, hyperfibrinolysis, and surgical bleeding. Check the activated clotting time and consider additional protamine for residual heparin; the "lethal triad" of hypothermia, acidosis, and coagulopathy must be corrected in parallel, not sequentially.

Drug-related bleeding and reversal

Device- and disease-related thrombocytopenia

Intra-aortic balloon pumps cause mechanical platelet destruction, usually a modest fall that recovers after removal. ECMO produces consumption, shear-mediated platelet dysfunction, and acquired von Willebrand syndrome simultaneously. Continuous renal replacement therapy circuits consume platelets and fibrinogen. Liver disease produces a rebalanced hemostatic state in which both procoagulants and anticoagulants fall — the INR in cirrhosis does not predict bleeding and should not be "corrected" reflexively before procedures.

Product thresholds and viscoelastic testing

Viscoelastic testing (thromboelastography, TEG, or rotational thromboelastometry, ROTEM) shows the whole clot in real time and directs targeted therapy rather than shotgun transfusion:

• Prolonged R time / CT = factor deficiency, treat with plasma or PCC
• Prolonged K time, reduced alpha angle / CFT = fibrinogen deficiency, treat with cryoprecipitate or fibrinogen concentrate
• Reduced maximum amplitude (MA) / MCF = platelet number or function problem, treat with platelets, and consider desmopressin
• Elevated LY30 / ML = hyperfibrinolysis, treat with an antifibrinolytic
• A heparinase-treated channel that normalizes identifies residual heparin, which is treated with protamine, not plasma

Algorithm-guided viscoelastic management reduces transfusion in cardiac surgery and is recommended in patient blood management guidance.

Nursing bleeding surveillance

Trend hemoglobin and platelets against the admission baseline, not the last value. Quantify chest tube drainage hourly — more than 200 mL/hr for 2 consecutive hours or more than 300 mL in any single hour warrants surgical notification, and an abrupt cessation of previously brisk drainage with rising filling pressures, narrowing pulse pressure, and equalizing diastolic pressures signals tamponade, not improvement. After femoral arterial access, unexplained hypotension with flank or back pain and a falling hemoglobin without an obvious external source is retroperitoneal hemorrhage until imaging says otherwise. Add routine stool guaiac in anticoagulated patients, serial neurologic checks, site and dressing checks each shift, minimized venipuncture and arterial punctures, soft toothbrushes and electric razors, no intramuscular injections, and proton pump inhibitor prophylaxis for patients on dual antiplatelet therapy with additional risk factors.