Introduction

Thrombophilia denotes a constitutional predisposition to thrombosis; thrombophilic traits may be genetic or acquired. It has not been standard practice to grade thrombophilia by severity, but such a grading could have practical clinical import. Grading of thrombophilia may be performed in a number of ways. The severity of thrombophilia may be regarded as the magnitude of the risk for first (incident) thrombosis, risk for thrombus recurrence or risk for poor thrombotic outcomes such as death or post-thrombotic syndrome. Severity of thrombophilia may also denote the clinical severity of the thrombotic episode, such as thrombotic storm or purpura fulminans. “Thrombophilia,” if extended to the larger context of prothrombotic risk beyond blood-based predisposing factors, can also be anatomic, such as external venous compression (e.g., Paget–Schroetter, May–Thurner); however, we will focus in this chapter on hematologic thrombophilia. This includes enhanced procoagulants, diminished anticoagulants and diminished fibrinolysis as mechanisms leading to increased thrombosis.

Genetic thrombophilic traits judged to be more potent often present at an earlier age or manifest recurrence soon after discontinuation of anticoagulation for a previous event. Patients with severe thrombophilia may spontaneously initiate a thrombotic event, while most experience a provoking trigger, tipping the balance in favor of thrombosis. However, the severe thrombophilias may require only a slight trigger (i.e., a mild upper respiratory infection), which may result in sustained activation of coagulation and progressive thrombosis even despite conventional antithrombotic drugs at typical target anticoagulant activity and duration. In this chapter we attempt to describe the subset of pediatric thrombotic syndromes that are clinically very severe and require a high index of suspicion, prompt diagnosis and immediate institution of appropriate therapy for a favorable outcome.