Bleeding
Ellis J. Neufeld
The hemostatic mechanism in the neonate differs from that in the older child. In neonates, there is decreased activity of several clotting factors, diminished platelet function, and suboptimal defense against clot formation. A detailed review of the subject is provided in reference (1).
I. ETIOLOGY
Deficient clotting factors
Transitory deficiencies of the procoagulant vitamin K—dependent factors II, VII, IX, and × and anticoagulant proteins C and S are characteristic of the newborn period and may be accentuated by the following:
The administration of total parenteral alimentation or antibiotics or the lack of administration of vitamin K to premature infants.
Term infants may develop vitamin K deficiency by day 2 or 3 if they are not supplemented with vitamin K parenterally because of negligible stores and inadequate intake.
The mother might have received certain drugs during pregnancy that can cause bleeding in the first 24 hours of the infant’s life.
Phenytoin (Dilantin), phenobarbital, and salicylates interfere with the vitamin K effect on synthesis of clotting factors.
Warfarin and related compounds given to the mother interfere with the synthesis of vitamin K—dependent clotting factors by the livers of both the mother and the fetus, and the bleeding may not be immediately reversed by administration of vitamin K.
Disturbances of clotting may be related to associated diseases, such as disseminated intravascular coagulation (DIC), due to infection, shock, anoxia, necrotizing enterocolitis (NEC), renal vein thrombosis (RVT), or the use of vascular catheters. Any significant liver disease may interfere with the production of clotting factors by the liver.
Inherited abnormalities of clotting factors
X-linked recessive (expressed predominantly in males; affected females should raise concern for Turner syndrome, partial × deletions, or nonrandom X-chromosome inactivation):
Factor VIII levels are decreased in the newborn with hemophilia A (1 in 5, 000 boys) (4).
Hemophilia B or Christmas disease is due to an inherited deficiency of factor IX (1 in 25, 000 boys) (4).
One-third of patients with severe hemophilia express “new mutations,” so family history alone cannot rule out the problem.
Autosomal dominant (expressed in boys and girls with one parent affected):
Von Willebrand disease (VWD) is due to decreased levels or functional activity of von Willebrand factor (VWF), which acts as a carrier for factor VIII and as a platelet-aggregation agent. VWD is the most common inherited coagulation defect (up to 1% of the population as assayed by factor levels) (4). Neonatal levels of VWF are elevated in normal babies compared with older children and nonpregnant adults because of maternal estrogen.
Dysfibrinogenemia (very rare) is due to fibrinogen structural mutations.
Autosomal recessive (occurs in both boys and girls born to carrier parents). In order of frequency, deficiencies of factors XI, VII, V, X, II, fibrinogen, and XIII are all encoded by autosomal genes. Factor XII is a special case because deficiency causes long partial thromboplastin time (PTT) but never causes bleeding. Combined factors V and VIII deficiency is caused by defect in the common processing protein ERGIC-53 (5).
Severe factor VII or factor XIII deficiency can present as intracrania l hemorrhage in neonates.
Factor XI deficiency is incompletely recessive because heterozygotes may have unpredictable bleeding problems with surgery or trauma.
VWD type III (rare, complete absence of VWF) (4).
Platelet problems (see Chap. 47)
Qualitative disorders include hereditary conditions (e.g., storage pool defects, Glanzmann thrombasthenia, Bernard-Soulier syndrome, platelet-type VWD (6) and transient disorders that result from the mother’s use of antiplatelet agents.
Quantitative disorders include the following:
Immune thrombocytopenia (maternal idiopathic thrombocytopenic purpura [ITP] or neonatal alloimmune thrombocytopenia [NAIT]) (7).
Maternal preeclampsia or HELLP syndrome (see Chap. 4), or severe uteroplacental insufficiency.
DIC due to infection or asphyxia.
Inherited marrow failure syndromes, including Fanconi anemia and congenital amegakaryocytic thrombocytopenia.
Congenital leukemia.
Inherited thrombocytopenia syndromes, including gray platelet syndrome and the macrothrombocytopenias, such as May-Hegglin syndrome (6).
Consumption of platelets in clots or vascular lesions without DIC. Examples include vascular malformations, notably Kasabach-Merritt phenomenon from kaposiform hemangioendotheliomas; thrombosis from catheters; RVT; and NEC.
Heparin-induced thrombocytopenia (HIT) deserves special consideration for several reasons. First, this condition leads to platelet activation and risk of thrombosis more than bleeding. Second, it is probably rare in neonates, although the antibody can be detected by ELISA assays after cardiac surgery. Finally, in neonates, the antibody may be maternal, as with other antibodies passed across the placenta.
Other potential causes of bleeding are vascular in etiology and may include central nervous system hemorrhage, pulmonary hemorrhage, arterio-venous malformations, and hemangiomas.
Miscellaneous problems
Trauma (see Chap. 6)
Rupture of spleen or liver associated with breech delivery.
Retroperitoneal or intraperitoneal bleeding may present as scrotal ecchymosis.
Subdural hematoma, cephalhematoma, or subgaleal hemorrhage (the latter may be associated with vacuum extraction).
Liver dysfunction.
II. DIAGNOSTIC WORKUP OF THE BLEEDING INFANT
The history includes (i) family history of excessive bleeding or clotting, (ii) maternal medications (e.g., aspirin, phenytoin), (iii) pregnancy and birth history, (iv) maternal history of a birth of an infant with a bleeding disorder, and (v) any illness, medication, anomalies, or procedures done to the infant.
Examination. The crucial decision in diagnosing and managing the bleeding infant is determining whether the infant is sick or well (see Table 43.1).
Sick infant. Consider DIC, viral or bacterial infection, or liver disease (hypoxic/ischemic injury may lead to DIC).
Well infant. Consider vitamin K deficiency, isolated clotting factor deficiencies, or immune thrombocytopenia. Maternal blood in the infant’s gastrointestinal (GI) tract will not cause symptoms in the infant.
Petechiae, small superficial ecchymosis, or mucosal bleeding suggests a platelet problem.
