• New York State Department of Health. HIV-related hematologic manifestations in pediatrics. New York (NY): New York State Department of Health; 2003. 12 p. [14 references]

This is the current release of the guideline.

Screening for Hematologic Abnormalities

A complete blood count with differential should be performed every 3 months to screen for hematologic abnormalities in human immunodeficiency virus (HIV)-infected children. Complete blood count may need to be obtained more often for children receiving bone marrow suppressive therapy or if abnormalities are identified.

Anemia

Types of Anemia

Microcytic Anemia

The diagnostic evaluation for microcytic anemia in the HIV-infected child should include a careful nutritional history, review of systems (especially the gastrointestinal tract), and iron studies, specifically serum iron, total iron-binding capacity, transferrin saturation, and serum ferritin. If indicated by family history or if the anemia persists after a therapeutic trial of iron, hemoglobin electrophoresis with quantitative measurement of hemoglobin A2 and hemoglobin F should be performed.

Screening of lead levels should be performed yearly in all children and whenever toxicity is suspected.

Normocytic Anemia

Hemolytic Anemia

Evaluation for hemolysis should be performed in individuals with unusually high transfusion requirements or those with high reticulocyte count, low serum haptoglobin (only for intravascular hemolysis), presence of microspherocytes on the peripheral smear, indirect hyperbilirubinemia, or bone marrow erythroid hyperplasia.

Hypoplastic Anemia

If a patient presents with hypoplastic anemia in the presence of fever, weight loss, or new physical findings, opportunistic infections should be excluded. Appropriate cultures and bone marrow examination should be performed to help establish the diagnosis.

Macrocytic Anemia

If megaloblastic anemia cannot be explained by common causes, such as medications, including antiretroviral (ARV) drugs, evaluation should include liver and thyroid function tests, vitamin B12 and folate levels, bone marrow aspiration, and biopsy to evaluate for the possibility of bone marrow failure or myelodysplasia.

Treatment of Anemia

If endogenous erythropoietin levels are <500 mUnits/mL, erythropoietin therapy (50-200 iu/kg/dose 3 times/week) should be administered to reduce the need for transfusion. Supplemental oral iron (3-6 mg/kg/day of elemental iron) and folate (1 mg/day) should be administered when erythropoietin is initiated.

If clinically significant anemia (i.e., hemoglobin <7 g/dL or cardiorespiratory compromise) develops within the first month of life and zidovudine prophylaxis, the use of erythropoietin or transfusion is recommended to allow sustained use of zidovudine until the diagnosis of perinatal infection has been established. The zidovudine dose should not be modified.

If severe anemia develops after the fourth week of zidovudine prophylaxis, zidovudine may be discontinued at that time rather than subjecting the neonate to blood transfusion or erythropoietin.

The necessity for blood transfusion should be evaluated carefully. Transfusions should be reserved for clinically significant, severe anemia. Irradiation and leukocyte reduction of blood according to standard protocols should be used for all transfusions.

Thrombocytopenia

Pathophysiology and Diagnosis

If thrombocytopenia is identified, the differential diagnosis should be established according to the presence or absence of one or more of the following:

• abnormalities in the physical examination, especially organomegaly or lymphadenopathy
• abnormalities in the non-platelet components of the complete blood count
• failure to respond to platelet-directed treatment

If physical examination abnormalities or multiple cell line deficits are present or if the platelet count does not respond to platelet-directed treatment, prompt investigation for infectious, toxic, or malignant causes should be performed.

A bone marrow examination should be performed in consultation with a hematologist/ oncologist when malignancy is suspected.

If thrombocytopenia is accompanied by other cytopenias or splenomegaly and is mild (>50,000 cells/mm³), hypersplenism caused by infectious causes or coincident liver disease should be suspected.

Treatment of Thrombocytopenia

Antiretroviral therapy should be the primary treatment of HIV-associated thrombocytopenic purpura unless 1) it has been previously demonstrated to be ineffective, 2) the count needs to be increased within 2 weeks, or 3) there are other reasons not to initiate it, such as refusal, intolerance, or limited antiretroviral susceptibility. Treatment of asymptomatic, mild to moderate, HIV-associated thrombocytopenia is usually not necessary. When the platelet counts are <20,000 to 30,000 cells/mm³, treatment should be initiated in consultation with a hematologist. Treatment should be initiated in patients with bleeding tendencies such as hemophilia when the platelet count is <50,000 cells/mm³.

For most patients who need treatment for HIV-associated thrombocytopenia, the treatment of choice is intravenous anti-Rho immunoglobulin (IV anti-D), 50 micrograms/kg with premedications.

For patients unable to receive anti-D because they are either Rh(–), DAT(+), or have undergone a splenectomy, intravenous immunoglobulin (1 g/kg) is the next best treatment. Prednisone has also been effective in treating thrombocytopenia and may be administered once malignancy has been ruled out.

Neutropenia

Treatment of Neutropenia

If neutropenia is confirmed to be persistent and severe (<500 cells/mm³), rather than transient, consideration should be given to instituting granulocyte-colony stimulating factor (G-CSF). The initial dose is 5 micrograms/kg/day given subcutaneously. The G-CSF dosing required varies greatly from person to person; dosing frequency should be titrated to an individual's response. In children with multiple cell line deficits, G-CSF may exacerbate thrombocytopenia; therefore, platelet counts should be monitored. Bone marrow aspiration before initiating G-CSF therapy is not necessary unless there is also evidence of anemia, thrombocytopenia, new lymphadenopathy, or hepatosplenomegaly.

Coagulation Abnormalities

Diagnosis

The preoperative evaluation of bleeding tendency should include a medical history, physical examination, and, if indicated, basic hemostatic screening tests. The information obtained in the medical history should include the presence of abnormal bruising, both extensive or unexplained; gum bleeding; prolonged bleeding after laceration or surgery, such as circumcision, tonsillectomy, tooth extractions, or biopsies; epistaxis; menorrhagia; hematuria; and melena in the patient and in the family. In addition, information regarding liver or renal disease or changes in medication in the HIV-infected patient should be obtained.

Routine pre-operative bleeding screening tests, such as a partial thromboplastin time (PTT), prothrombin time (PT), fibrinogen platelet count, and thrombin time, should be reserved for patients with a positive assessment by history or those with a negative history who will be undergoing surgeries with a high risk of bleeding, such as tonsillectomy, central nervous system surgery, cardiac surgery, or scoliosis repair.

When a prolonged PTT is present, mixing studies (1:1 dilution with normal plasma) should be obtained. Failure to correct a prolonged PTT should be indicative of the presence of antiphospholipid antibodies (aPL) or specific factor inhibitors. If the mixing studies reveal correction, assays for factors VIII, IX, XI, and XII should be performed.

Primary hemostasis tests, including von Willebrand factor (vWF) studies, platelet aggregation, factors VIII, IX, XI, XIII, alpha 2-antiplasmin and plasminogen activator inhibitor (PAI), should be obtained for patients with normal PT, PTT, fibrinogen, and platelet count who are at high risk for bleeding based on history. Neither the bleeding time nor the Platelet Function Analyzer (PFA)-100 is recommended because of the absence of data to support that these tests predict bleeding.

Treatment of Coagulation Abnormalities

Treatment of HIV-associated coagulation abnormalities should be based on the specific diagnosis as well as bleeding history (see Table below).

Table: General Therapeutic Options for Treating Coagulation Abnormalities in HIV-infected Children

None provided

The type of evidence supporting the recommendations is not stated.

• New York State Department of Health. HIV-related hematologic manifestations in pediatrics. New York (NY): New York State Department of Health; 2003. 12 p. [14 references]

Not applicable: The guideline was not adapted from another source.

2003

New York State Department of Health - State/Local Government Agency [U.S.]

New York State Department of Health

Committee for the Care of Children and Adolescents with HIV Infection

Committee Chair: Joseph S. Cervia, MD, Director, The Comprehensive HIV Care and Research Center, Long Island Jewish Medical Center

Committee Vice Chair: Jeffrey M. Birnbaum, MD, MPH, Director, HEAT Program, Kings County Hospital

Committee Members: Elaine Abrams, MD, Director, Family Care Center, Department of Pediatrics, Harlem Hospital Center; Saroj Bakshi, MD, Chief, Division of Pediatric Infectious Diseases, Bronx-Lebanon Hospital Center; Howard J. Balbi, MD, Director, Pediatric Infectious Diseases and Pediatric AIDS Program, Nassau County Medical Center; Coleen K. Cunningham, MD, Associate Professor of Pediatrics, SUNY Upstate Medical University; Samuel Grubman, MD, Chief, Allergy and Immunology, Saint Vincents Catholic Medical Centers, St. Vincent's Manhattan; Sharon Nachman, MD, Chief, Pediatric Infectious Diseases, Associate Professor of Pediatrics, SUNY at Stony Brook. Department of Pediatrics; Catherine J. Painter, MD, PhD, Assistant Professor of Clinical Pediatrics, College of Physicians and Surgeons, Columbia University, Medical Director, Incarnation Children's Center; Vicki Peters, MD, Coordinator, Pediatric HIV Special Projects, Office of AIDS Surveillance, New York City Department of Health; Roberto Posada, MD, Assistant Professor of Pediatrics, Division of Pediatric Infectious Diseases, Director, Pediatric HIV Program, Mount Sinai School of Medicine; Barbara Warren, BSN, MPH, PNP, Assistant Bureau Director, Bureau of HIV Ambulatory Care Services, AIDS Institute, New York State Department of Health; Geoffrey A. Weinberg, MD, Director, Pediatric HIV Program, Associate Professor of Pediatrics, Department of Pediatrics, University of Rochester School of Medicine and Dentistry; Ed Handelsman, MD, Assistant Professor of Pediatrics, SUNY Health Sciences Center at Downstate, Assistant Medical Director of Pediatrics, Office of the Medical Director, AIDS Institute

Not stated

This is the current release of the guideline.

None available

This summary was prepared by ECRI on January 21, 2004. This summary was updated by ECRI on January 31, 2006, following release of a public health advisory from the U.S. Food and Drug Administration regarding the use of WinRho SDF (Rho(D) Immune Globulin Intravenous [Human]). This summary was updated by ECRI on January 29, 2007, following the U.S. Food and Drug Administration advisory on erythropoiesis stimulating agents. This summary was updated by ECRI Institute on July 9, 2007, following the FDA advisory on erythropoiesis stimulating agents. This summary was updated by ECRI Institute on December 7, 2007, following the U.S. Food and Drug Administration advisory on Desmopressin Acetate. This summary was updated by ECRI Institute on March 21, 2008 following the FDA advisory on Erythropoiesis Stimulating Agents. This summary was updated by ECRI Institute on August 15, 2008 following the U.S. Food and Drug Administration advisory on Erythropoiesis Stimulating Agents (ESAs).