14.2 Pediatric Coagulopathies, Disseminated Intravascular Coagulation (DIC) & Thrombosis

Pediatric Coagulopathies and Thrombosis

Quick Answer: With acute bleeding or thrombosis, assess perfusion, the bleeding site, trends in blood counts and coagulation, and the underlying illness. Treat the cause of DIC and replace specific deficits when clinically indicated. Distinguish isolated thrombocytopenia from a thrombotic microangiopathy. Symptomatic DVT usually warrants anticoagulation after review of bleeding risk.

How Platelets and Coagulation Interact

At vascular injury, von Willebrand factor (vWF) helps platelets adhere through the GPIb complex. Activated platelets aggregate through GPIIb/IIIa and fibrinogen. In the cell-based model, coagulation occurs in three overlapping stages:

1. Initiation: Tissue factor with factor VIIa activates factors IX and X, enabling a small amount of thrombin generation on a tissue factor-bearing cell.
2. Amplification: Thrombin activates nearby platelets and cofactors and helps prepare the platelet surface for further coagulation.
3. Propagation: On activated platelets, factor IXa with VIIIa activates X. Factor Xa with Va generates a burst of thrombin. Thrombin converts fibrinogen to fibrin, and factor XIIIa crosslinks fibrin to stabilize the clot.

PT and aPTT assess selected plasma pathways. Interpret the results alongside platelet count, fibrinogen and the clinical pattern. Cell-based hemostasis model · Mechanistic study

Disseminated Intravascular Coagulation

DIC is an acquired systemic process associated with a trigger such as sepsis, major trauma or malignancy. Coagulation activation, endothelial injury and dysregulated fibrinolysis can produce microthrombi and organ dysfunction. Consumption can cause thrombocytopenia, falling fibrinogen and bleeding, including catheter-site oozing, purpura or hematuria. The balance of thrombosis and bleeding varies with the cause and phase. Fibrinogen may initially remain in the reference range because it is an acute-phase reactant. Follow the trajectory and assess competing causes such as liver dysfunction, dilution or drug effects. ISTH 2025 DIC communication

Apply the 2025 ISTH overt DIC score in context

Use the score with a compatible underlying disorder. Calculate the D-dimer multiple using the lab's upper normal limit in matching units and assay, and PT prolongation relative to the lab control or reference used by the local scoring protocol. Select only the highest applicable category within each row. ISTH 2025 score, Table 1

A total of 5 or more supports overt DIC with a compatible clinical trigger. A lower score can occur early. Repeat assessment and laboratory trends according to clinical evolution. The 2025 ISTH communication replaced qualitative D-dimer categories with assay-relative thresholds. Pediatric studies of the earlier and revised scores support interpreting results in context. A U.S. pediatric series found that serial measurements improved sensitivity with the older score. A 2026 observational PICU comparison found close agreement between the revised and older overt scores, but identification varied by scoring system and subgroup. The score is neither a pediatric sepsis definition nor a transfusion trigger. Pediatric serial assessment study · 2026 pediatric comparison

Worked example. In a bleeding child with septic shock, a platelet count of 28,000/µL scores 2, D-dimer 4.0 with upper limit 0.5 in the same units scores 3 (8×), PT 24.8 seconds with a 12.0-second control scores 2 (12.8 seconds longer), and fibrinogen 74 mg/dL scores 1. The total is 8. Treat the infection and support perfusion. Cryoprecipitate is a concentrated source of fibrinogen for the severe deficiency with active bleeding. Select its dose by product and local practice and recheck bleeding and fibrinogen.

Treat the cause and the bleeding

Control the trigger, for example by timely antimicrobials and source control in septic DIC. For significant bleeding, discuss targeted replacement with hematology and transfusion medicine. Consider cryoprecipitate or fibrinogen concentrate for severe hypofibrinogenemia, plasma when multiple factor deficits contribute, and platelets when thrombocytopenia contributes. Pediatric TAXI-CAB suggests that platelets may be considered below 50,000/µL with moderate bleeding in sepsis/DIC, based largely on indirect evidence. Without moderate or severe bleeding, prophylactic plasma may offer no benefit. For that setting TAXI-CAB allows consideration of platelets below 10,000/µL. Bleeding site, procedures, platelet function and clinical trajectory can change management. Use the established pediatric blood product guidance and monitor the clinical response. Pediatric TAXI-CAB · AABB Circular

Pediatric Venous Thromboembolism

Central venous catheters are an important pediatric VTE risk factor. Other risks include immobility, surgery, congenital heart disease, infection, malignancy and asparaginase exposure. For unilateral limb swelling or discoloration, use duplex ultrasound first. If the central or pelvic extent is unclear, discuss CT or MR venography. Echocardiography can assess an intracardiac clot. Suspected cerebral venous thrombosis requires dedicated venous imaging. CHOP catheter-related VTE pathway · ASH/ISTH pediatric VTE guideline

The ASH/ISTH 2024 update, published in 2025, conditionally favors anticoagulation for symptomatic DVT or PE. Weigh bleeding and thrombosis risk, especially after neonatal procedures or with catheter-associated thrombi. A needed, functioning catheter can often remain in use during treatment. If an unneeded or nonfunctional catheter needs removal, coordinate the timing based on clot burden and embolization risk. Selected low-risk provoked VTE can qualify for six weeks of treatment. PE, recurrent VTE, persistent occlusion at six weeks, cancer, major thrombophilia or other ongoing risk factors may require longer treatment. ASH/ISTH pediatric VTE guideline

• Enoxaparin: The 2024 ASH/ISTH update gives starting examples of 1.5–1.7 mg/kg subcutaneously every 12 hours below three months and 1 mg/kg every 12 hours above five years, with intermediate age bands and subsequent titration. Some neonatal protocols use higher doses, particularly for preterm infants. For twice-daily therapeutic dosing, use peak anti-Xa 0.5–1.0 IU/mL. Follow the local sampling schedule. Children's Mercy obtains the initial level four hours after the third dose. Check renal function, bleeding risk and a preservative-free preparation in neonates. The U.S. Lovenox label states that pediatric safety and effectiveness have not been established. ASH/ISTH guideline · Children's Mercy enoxaparin pathway · Preterm dosing cohort · U.S. Lovenox label
• Unfractionated heparin: Useful when rapid interruption may be needed or in selected renal impairment. Use the institution's age-adjusted infusion and monitoring protocol. A commonly used anti-Xa target is 0.35–0.70 IU/mL or a locally correlated aPTT. Consider bleeding risk before a loading bolus. Protamine reverses UFH more completely than LMWH. ASH/ISTH guideline
• Direct oral anticoagulants: ASH/ISTH conditionally favors rivaroxaban or dabigatran over standard options in eligible children. For pediatric VTE treatment, U.S. labeling requires at least five days of initial parenteral treatment before either agent. Product-specific age, weight, formulation, organ function and other restrictions apply. ASH/ISTH guideline · U.S. rivaroxaban label · U.S. dabigatran label

When a platelet fall or new thrombosis raises concern for heparin-induced thrombocytopenia, assess exposure and alternative causes. Consult hematology promptly about stopping heparin and choosing a nonheparin anticoagulant such as bivalirudin or argatroban when indicated. Pediatric HIT is uncommon, and drug choice and monitoring depend on the clinical setting and organ function. ASH HIT guideline

Distinguish ITP, TTP and STEC-HUS

Immune thrombocytopenia (ITP)

Isolated thrombocytopenia with otherwise reassuring CBC and smear in a well-appearing child with petechiae or bruising suggests ITP. Review medications, infections, other cytopenias and exam findings that suggest alternate diagnoses. For newly diagnosed ITP with absent or minor skin bleeding, observation and timely follow-up are usually appropriate. For noncritical mucosal bleeding or reduced quality of life, ASH favors a short corticosteroid course when appropriate, for example prednisone 2–4 mg/kg/day, maximum 120 mg/day, for 5–7 days. IVIG is an alternative when a faster rise is needed or steroids are unsuitable. Critical bleeding such as intracranial hemorrhage or hemodynamically significant hemorrhage requires emergency hematology treatment. A 2026 multidisciplinary guideline supports combined high-dose steroids, IVIG and platelet transfusion for a critical ITP bleed with severe thrombocytopenia, with tranexamic acid and a thrombopoietin receptor agonist as appropriate under the emergency plan. ASH ITP guideline · 2026 critical bleeding guideline

Thrombotic thrombocytopenic purpura (TTP)

Microangiopathic hemolysis (schistocytes, high LDH and low haptoglobin), thrombocytopenia and neurologic or other organ injury raise concern for TTP. PT and aPTT may be normal. Severe ADAMTS13 activity below 10% supports TTP. Draw activity and inhibitor or anti-ADAMTS13 antibody samples before plasma therapy when feasible. With high suspicion for immune TTP, involve hematology and begin urgent plasma exchange and corticosteroids without waiting for the result. Hematology considers rituximab and caplacizumab according to likelihood, disease course and bleeding risk. Avoid prophylactic platelet transfusion. Life-threatening bleeding requires specialist judgment. ISTH diagnosis guideline · ISTH 2025 TTP update

The U.S. caplacizumab label includes acquired TTP at age 12 years and older with plasma exchange and immunosuppression. It blocks vWF-mediated platelet adhesion and increases bleeding risk. Congenital TTP is treated with ADAMTS13 replacement. Recombinant ADAMTS13 is approved for prophylactic and on-demand treatment in children and adults with congenital TTP. Its September 2026 U.S. boxed warning concerns neutralizing antibodies and serious outcomes. Monitor ADAMTS13 activity and neutralizing antibodies before starting and periodically during treatment under the label. U.S. Cablivi label · U.S. Adzynma label

Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS)

Shiga toxin-associated endothelial injury can cause microangiopathic hemolytic anemia, thrombocytopenia and AKI after diarrheal illness. Bloody diarrhea is a clue. Send stool testing for STEC and assess other causes when the presentation is atypical. Monitor volume status, urine output, blood pressure and electrolytes. Provide supportive care and kidney replacement therapy when indicated. Early hydration in diarrheal STEC infection is distinct from fluid management once oliguric AKI develops. Avoid antimotility drugs and antibiotics directed at suspected O157, Shiga toxin 2-producing or toxin-genotype-unknown STEC. Evaluate independent indications for antimicrobials separately. CDC STEC clinical guidance · IDSA infectious diarrhea guideline