Hematologic abnormalities are frequently encountered in the ill pediatric patient. Many excellent reviews of the physiology and pathophysiology of blood disorders and coagulation are currently available. This chapter is designed to complement rather than replace them. The goal is to provide a practical guide for the practicing surgeon and to aid in the formulation of diagnostic and treatment algorithms for the care of actual patients.

In the strictest sense, anemia is defined as a hemoglobin value or hematocrit level that is below 2 standard deviations from the mean for a given patient’s age and sex. This definition, however, does not serve to identify those patients with clinically significant reductions in RBC mass, which is usually defined as the level at which tissue oxygenation is compromised. In fact, most decisions to transfuse RBCs are based on clinical judgment, currently available clinical and experimental data, accepted clinical guidelines, and personal experience.

The range of “normal” hematocrit levels for a particular age group can be rather broad. Likewise, the acceptable minimum hematocrit for any given patient is variable. In general, red cell transfusion is not considered in an otherwise healthy asymptomatic child until the hematocrit is less than approximately 21% (hemoglobin <7.0 g/dL). Even this is not an absolute indication for transfusion, as we have seen healthy children tolerate levels less than this with minimal physiologic embarrassment. Furthermore, in stable critically ill children, a recent randomized controlled trial demonstrated that a hemoglobin level of 7 g/dL is feasible as a transfusion threshold without affecting outcome. Some children with chronic anemia (eg, chronic renal insufficiency) have established compensatory mechanisms to such a degree that they can tolerate hematocrit levels much lower than those stated above. On the other hand, children with a hematocrit value higher than a minimally acceptable standard but who are clinically compromised may require transfusion regardless of the absolute hematocrit.

Newborns have a hematocrit value that normally varies between 47% and 60% but gradually decreases to a “physiological nadir” at approximately 2 to 3 months of age. This value can be as low as 28% in healthy infants. This nadir also coincides with the normal replacement of fetal hemoglobin (HbF), the predominant form in neonates, with the adult type. HbF has a higher affinity for oxygen and demonstrates a relative left shift of the oxygen–hemoglobin dissociation curve. Congenital hemoglobinopathies affecting the adult form of hemoglobin (eg, sickle cell anemia, thalassemia, etc) typically become clinically apparent after 2 to 3 months, when most of the unaffected HbF has been replaced with the defective adult form. Healthy newborns are not transfused unless they are clinically compromised by a low hematocrit. Critically ill neonates, especially premature infants, are often empirically transfused to hematocrit levels of 30% or higher depending on the clinical scenario.

There are accepted indications for empiric blood transfusion in the setting of acute blood loss typically encountered in the trauma bay or operating room. Most protocols suggest transfusion for acute losses that result in hypotension or mental status changes. In some truly emergent circumstances, it may be necessary to transfuse type-specific or type O blood because of the time required to properly cross-match units of blood.

There is no universally accepted standard for an “optimal” hematocrit level for a given patient about to undergo elective surgery. The decision regarding preoperative transfusion is thus often made jointly by the surgeon and anesthetist, who consider the age and cardiorespiratory status of the patient, the nature of the procedure, anticipated blood loss, and the patient’s baseline hematocrit. In general, a preoperative hematocrit value of approximately 30% would be considered a safe and adequate level for major procedures in most patients.

Blood volume varies according to age from approximately 70 mL/kg in adults to 80 mL/kg in newborns and up to 90 mL/kg in premature infants. We use 80 mL/kg as a convenient estimate for newborns and children up to 30 kg. A typical blood transfusion volume in children is between 10 and 15 mL/kg of packed RBCs, depending on the indication. The expected change in hematocrit for a given volume of transfusion can be estimated by the formula: (volume transfused × hematocrit of transfused blood)/blood volume. Because the hematocrit of packed RBCs is approximately 50% to 60%, one should expect in the absence of ongoing bleeding a rise in hematocrit of approximately 6 to 8 points for every 10 mL/kg of packed RBCs transfused. Patients who have less than the calculated expected rise should be evaluated for ongoing bleeding or hemolysis.

Efforts to minimize transfusions for elective adult surgery have led to several strategies that are being tested in the pediatric surgical population. First, acute normovolemic hemodilution typically involves pre- or intraoperative removal of whole blood and replacement with a crystalloid solution. With subsequent intraoperative bleeding, the hemodiluted patient will thus lose less hemoglobin per milliliter of blood lost. The previously removed whole blood can be transfused back as needed. Next, devices that process and return blood lost during surgery are in developmental and experimental stages for infants and children. Also, preoperative administration of erythropoietin and the use of deliberate hypotension are being employed in selected circumstances. It is believed that a combination of some or all of these techniques will help minimize or even eliminate the need for allogenic transfusions in the future.

Normal adult hemoglobin is composed of two pairs of globin subunits, each in turn made up of an α chain and a β chain. The common hemoglobinopathies consist of defective β-chain subunits in which the normal β chains (hemoglobin A) are replaced by one or more of sickle cell, hemoglobin C, or β-thalassemia β chains. Patients with SCD include those who are homozygous for sickle cell (hemoglobin SS disease) as well as those who are doubly heterozygous for sickle cell and hemoglobin C disease (hemoglobin SC disease) or β-thalassemia (hemoglobin Sβ disease).

Persons with the heterozygous sickle cell trait are generally asymptomatic while those with homozygous disease generally have severe alterations of RBC function. These result in increased cell rigidity and adherence, with the potential for conversion to an elongated “sickle” shape due to polymerization of the abnormal hemoglobin. Sickling is induced by hypoxia, acidosis, dehydration, or hyperosmolarity. This is clinically manifest by vasoocclusive “crises,” which are extremely painful and can result in tissue injury and organ dysfunction.

Crises can occur anywhere in the body and are frequently recurrent and characteristic in a given individual. Painful abdominal crises can pose a diagnostic dilemma, as they often mimic acute surgical processes. Most patients with an acute abdominal crisis will have had similar episodes in the past, which can help avoid unnecessary surgery. Nevertheless, these patients must be observed very closely for signs of a true abdominal catastrophe.

Acute splenic sequestration typically causes a rapid fall in the hemoglobin level and platelet count. Complications include hypovolemic shock and death. Recurrent episodes of sequestration are an indication for splenectomy.

Patients with SCD who undergo elective surgical procedures usually require preoperative preparation to avoid complications of the disease during and after operation. This typically involves transfusion therapy to decrease the relative amount of sickle hemoglobin. Recommendations have varied, but an aggressive approach involving decreasing the level of hemoglobin S to less than 30% has been used for years in many centers. However, data from a large multicenter trial suggest that patients treated with a more conservative approach, involving transfusion to a hemoglobin level of 10 g/dL, have a similar incidence of SCD-related complications and fewer transfusion-related complications. During and after the procedure, it is important to avoid conditions that are known to be conducive to sickling. This often requires careful monitoring in an intensive care setting and early consultation with hematologists and intensivists. Atelectasis and hypoxia require aggressive management to avoid the acute chest syndrome. This potentially lethal complication is characterized by severe chest pain, tachypnea, fever, and pulmonary infiltrates on chest radiograph. The treatment is aggressive and includes intensive respiratory support and exchange transfusion. Other perioperative complications include sepsis, painful crises, and cerebrovascular accidents.

Hereditary spherocytosis is an inherited defect in a red cell membrane protein that results in increased red cell fragility and hemolytic anemia. Splenectomy relieves the hemolysis and is essentially curative. Affected children should undergo splenectomy after the age of 5 years to minimize the risk of postsplenectomy sepsis. If gallstones are detected by preoperative ultrasound, patients typically undergo cholecystectomy. By use of current minimally invasive techniques, cholecystectomy and splenectomy can be combined in a single laparoscopic procedure with very little morbidity.

A normal platelet count is between 150,000 and 400,000/mm³. In general, adequate hemostasis for most surgical procedures requires a platelet count of at least 50,000/mm³, and spontaneous bleeding typically occurs when the platelet count falls below 10,000/mm³. Although there are several known congenital syndromes that include thrombocytopenia as one of their features, most patients encountered in pediatric surgery have an acquired form of thrombocytopenia.

Sepsis is a common cause of thrombocytopenia in neonates. Platelet consumption is felt to play a large role, although bone marrow suppression seems likely to be involved as well. This is of special concern in patients who have had an operation and in premature infants, who are at significant risk of intraventricular hemorrhage. Autoimmune platelet destruction can also occur in newborns as a result of maternal antibodies directed at inherited paternal platelet antigens. Known as neonatal isoimmune thrombocytopenia, it is difficult to treat with random donor platelets because of the prevalence of the PL^A1 antigen, which is usually the target antigen. Maternal platelets can be used when necessary.

Recommendations vary according to individual preferences, but in general, platelet transfusion is recommended for neonates who have any degree of thrombocytopenia and who are actively bleeding, and for those with a platelet count less than 20,000/mm³. It is common practice to transfuse critically ill newborns for platelet counts less than 50,000/mm³. The usual replacement dose is 10 mL/kg of standard random donor platelet concentrates.

Idiopathic thrombocytopenic purpura (ITP) most commonly occurs in preschool-age children, but can occur in all age groups. Thought to be caused by an autoimmune process, the disease typically occurs in the setting of a viral illness. Most patients recover within 1 month, and almost all recover within 6 months of the diagnosis. Those with severe thrombocytopenia can be treated with corticosteroids or intravenous (IV) immune globulin (IgG), with good temporary results. Transfused platelets are destroyed rapidly. Splenectomy provides effective relief in most patients but is rarely necessary except in cases of life-threatening hemorrhage or refractory thrombocytopenia.

Thrombocytopenia can also be caused by certain classes of drugs such as sulfa antibiotics, phenothiazines, and antiseizure medications. This usually responds to withdrawal of the offending drug. Thrombocytopenia also commonly occurs in the setting of hematologic malignancy, caused by either the primary disease process (eg, leukemia) or its treatment. From the pediatric surgical standpoint, this becomes a problem when a surgical procedure is required. Central line placement is a common example and in general is felt to be safe with a platelet count of 50,000/mm³ or more. There are some patients, however, whose platelet counts cannot be raised significantly with random donor platelet transfusions. These patients may benefit from single-donor platelet transfusions or by having platelets transfused continuously during the procedure.

Aspirin and nonsteroidal antiinflammatory drugs cause an inhibition of platelet aggregation by inhibiting platelet cyclooxygenase and thus reducing levels of thromboxane A₂. The effect of these drugs is permanent for a given population of exposed platelets. The effect can last for up to 2 weeks, as the half-life for platelets in the circulation is 7 to 10 days. The effect can be reversed in cases of severe hemorrhage with platelet transfusion, assuming that a significant serum level of the drug is not present.

Other antiplatelet agents include glycoprotein IIb/IIIa inhibitors and theinopyridines. The former class of drugs prevents thrombin from binding to platelet receptors, interfering with platelet aggregation. The latter inhibits both aggregation and secretion via the ADP/P2Y12 receptor.

There are rare congenital causes of platelet dysfunction such as Glanzmann thrombasthenia and the Bernard–Soulier syndrome. These are characterized by a prolonged bleeding time and can be treated temporarily in cases of severe bleeding with platelet transfusion. Platelet dysfunction also occurs in the setting of significant uremia. Hemodialysis can help, but in the emergent setting cryoprecipitate or desmopressin can be used. Patients who have excessive bleeding during or immediately after hemodialysis may have received an excessive heparin dosage and should be considered for empiric protamine administration (1 mg of protamine sulfate for every 100 units of heparin).

The most common inherited disorder of hemostasis is von Willebrand disease with a prevalence of approximately 1% in the general population. Clinically significant disease affects only approximately 0.1%, and the severe form of the disease is extremely rare. Several subtypes have been described, most of which are inherited as autosomal dominant traits. The disorder is caused by a quantitative and qualitative defect in von Willebrand factor (vWF), which mediates platelet adhesion and aggregation and acts as a carrier for plasma coagulation factor VIII. It is characterized by a family history of bleeding, a prolonged bleeding time, and a prolonged activated partial thromboplastin time (aPTT). The diagnosis can be confirmed by several in vitro tests. Patients with clinically mild forms of the disease who undergo minor surgical procedures may need no specific treatment. Desmopressin (DDAVP) improves bleeding times in certain patients with von Willebrand disease by causing a release of factor VIII from hepatic stores and vWF from endothelial cells. It is useful only for very minor operations and some dental procedures. Patients with more severe forms of von Willebrand disease and those who are to undergo major operative procedures can be treated with cryoprecipitate or vWF concentrates.