Chapter 92: Coagulation Disorders

INTRODUCTION

Bleeding and thrombosis are the 2 extremes of the physiologic process of coagulation disorders. Despite major differences in the levels of individual components of the hemostatic system, neonatal coagulation is equal to or somewhat more rapid than that observed in adults. This suggests the existence of a delicately balanced hemostatic system in neonates, with uncommon bleeding or thrombosis in healthy term infants. However, a number of perinatal or neonatal conditions can disrupt this balance and increase the risk for either hemorrhage or thrombus formation. The presence of bleeding in a healthy term or late preterm infant, especially in an infant with a normal platelet count, is strongly suggestive of a congenital bleeding disorder.

In general, coagulation disorders in the neonate can be classified as inherited bleeding disorders (hemophilia A and B, von Willebrand disease, or isolated factor II, VII, X, VIII, or XIII deficiencies) or acquired bleeding disorders (vitamin K deficiency bleeding, disseminated intravascular coagulation [DIC], liver disease, or extracorporeal life support related). The inherited disorders hemophilia A and B and von Willebrand disease account for 95% to 98% of congenital bleeding disorders.

PRINCIPLES OF HEMOSTASIS

I. NORMAL PHYSIOLOGY OF HEMOSTASIS

1. The primary phase. This is the production of the platelet plug. It involves platelet adhesion (to the injured vessel’s subendothelium) and their activation mediated by platelet surface glycoprotein (Ib, IIb/IIa) and von Willebrand factor (vWF).

2. The secondary phase. Results in the formation of a cross-linked fibrin clot. Coagulation proteins (factors XII to V) circulating as inactive precursor forms (zymogens) are converted to active forms through limited proteolysis. These activated proteins then further activate other zymogen factors in a chain reaction. Ultimately, the activation of factors V and X leads to cleavage of prothrombin (factor II) to thrombin (factor IIa). Cleavage of fibrinogen (factor I) to fibrin (factor Ia) by thrombin results in the formation of the blood clot.

3. The third phase. Modulates and limits the interactions of activated platelets and the clotting cascade (and Ca²⁺) that give rise to a clot. This includes the removal of activated factors (through the reticuloendothelial system) and the control of activated procoagulants by natural antithrombotic pathways (antithrombin III, protein C, protein S). Furthermore, restoration of vessel patency is triggered by the fibrinolytic pathway that generates plasmin from plasminogen. This is stimulated by tissue plasminogen activator (tPA) and limited by α₂-antiplasmin and plasminogen activator inhibitor. Plasmin is a proteolytic enzyme that degrades fibrin into fibrin split products such as D-dimers. Defects in fibrinolytic factors that result in excessive plasmin generation can lead to bleeding.

II. NEWBORN HEMOSTASIS

1. Neonatal platelets are reported to be hyporeactive; however, this deficiency is balanced by increased vWF activity, resulting in overall normal platelet function.

2. Factor VIII, factor V, fibrinogen, and factor XIII levels are normal at birth.

3. Vitamin K–dependent factors (II, ...