Easy Clotting

Background

Venous thromboembolism (VTE) has been recognized as a major secondary complication of infants receiving advanced tertiary care with complications ranging from fatal to serious long term morbidity including permanent neurological deficits. Hence, early diagnosis and proper treatment could make substantial difference in reducing the chance of these complications. This topic covers easy clotting in the newborn, infant and older child.

Basic Physiology

Stasis, endothelial injury and hyper-coagulability (Virchow’s triad) are the basic pathological mechanisms contributing to formation of VTE. 2/3 of VTE cases in children are associated with central venous lines (CVL) causing damage to vessel walls and disrupting blood flow. The inherited hypercoagulability state of infants has been also recognized as one of main contributors to VTE formation. The following inherited conditions were reported as the main causes of VTE cases:

Presentation

Risk factors for DVT

1. Family history of thrombosis
2. Personal history of VTE
3. Central line
4. Recent surgical procedures or trauma
5. History of immobilization or prolonged hospitalization/bed rest
6. Malignancy
7. Protein losing interopathy
8. Nephrotic syndrome
9. Hyperestrogenic state or Oral Contraceptive Pill use
10. Cigarette Smoking
11. Systemic Lupus Erytromatosis
12. Phospholipid antibody syndrome

Differential diagnosis of hyper-coagulable state:  

1. Inherited Causes

• Homocysteinuria (usually presents after newborn period)
• Proteine C and S deficiency (inhibits clotting by inactivating factors V and VIII)
• Prothrombin gene mutation
• Antithrombin deficiency
• Factor V Leiden. (altered factor V activity, resistant to antithrombotic effect of protein C)
• Antiphospholipid antibody syndrome (Lupus anticoagulant or Anticardiolipin antibodies)

2. Acquired Causes

• Presence of a CVL
• Immobilization
• Surgery (especially Ortho) or Trauma
• IBD
• Nephrotic syndrome
• Hemolytic anemia
• Decreased cardiac output
• Antiphospholipid antibody syndrome
• Malignancy
• Myeloproliferative disorders
• Leukocytosis in acute leukemia
• Pregnancy
• Estrogen

Procedures for Investigation

History

1. Recent surgery/ trauma / other issues as per risk factors above
2. Calf pain
3. Unilateral edema or swelling with a difference in calf diameters, warmth, tenderness, erythema, and/or superficial venous dilation
4. New onset acute hematuria (renal vein thromboses)

Physical exam

1. Palpable cord (reflecting a thrombosed vein)
2. Special attention to the vascular system, extremities (e.g., looking for signs of superficial or deep vein thrombosis)
3. Skin necrosis
4. There may be pain and tenderness in the thigh along the course of the major veins (“painful deep vein syndrome”)
5. Tenderness on deep palpation of the calf muscles is suggestive, but not diagnostic
6. Signs of hepatic vein thrombosis: ascites and hepatomegaly

Laboratory Studies

1. Complete blood count and platelet count
2. Renal function tests and urinalysis
3. Coagulation studies (prothrombin time, activated partial thromboplastin time)
4. Pro-coagulant panel: Prothrombin gene mutation, Antithrombin deficiency, Factor V Leiden, Protein C and S deficiency, Homocysteine levels, Lupus anticoagulant, anticardiolipin antibodies)
5. Ultrasound with Doppler
6. Consider appropriate imaging if pulmonary embolism suspected (beyond the scope of this topic review)

Resources

1. Pathogenesis and clinical manifestations of venous thrombosis and thromboembolism in infants and children. Manuela Albisetti, Anthony KC Chan, UpToDate
2. Approach to the diagnosis and therapy of deep vein thrombosis. Stephen A Landaw, Kenneth A Bauer, UpToDate
3. Diagnosis and treatment of venous thrombosis and thromboembolism in infants and children. Manuela Albisetti, Anthony KC Chan, UpToDate

Acknowledgements

Written by: Bahman Sotoodian

Editted by: Elmine Statham