Hematology and Oncology Disorders

Hematology and Oncology Disorders

Anemia: Acute

Christine A. Schindler


  • Increased red cell destruction (hemolysis) caused by hemoglobinopathies, membrane and enzyme defects, autoimmune hemolytic anemia, drug-associated hemolytic anemias, disseminated intravascular coagulation (DIC), and hemolytic uremic syndrome (HUS).

  • Excessive blood loss (hemorrhage).

  • Deficient red cell production (ineffective hematopoiesis).

    • Disorders of heme and globin production such as non-nutritional disorders of hemoglobin synthesis, thalassemia syndromes, lead poisoning, iron deficiency, chronic inflammatory diseases, chronic infections, chronic renal disease, and hyper/hypothyroidism.

Clinical Presentation

  • Weakness, fatigue, confusion, and palpitations.

  • Pallor, tachycardia, flow murmur, diminished peripheral pulses, and sometimes jaundice.

Diagnostic Evaluation

  • Marked decrease in hematocrit and hemoglobin.

  • RBC indices and morphology.

    • Increased reticulocyte count and low mean corpuscular volume (MCV) includes hemoglobinopathies (e.g., thalassemia syndromes).

    • Increased reticulocyte count and normal MCV indicates Membrane, Enzyme, or Immune disorders, Microangiopathic anemias, DIC, infection-induced hemolysis or chronic blood loss.

    • Low, normal, or slightly elevated reticulocytes and low MCV: iron deficiency anemia, lead toxicity, Thalassemia trait, Sideroblastic anemia, or anemia of chronic disease.

    • Low, normal, or slightly elevated reticulocytes, and high MCV: congenital hypoplastic or aplastic anemia, acquired hypoplastic or aplastic anemia (malignancies), aplastic crisis with underlying hemolytic anemia (HbSS), megoblastic anemia (Folate or B12 deficiency), immune disorders, Hypersplenism, anemia of chronic disease.


  • Treat underlying cause, maintain oxygenation.

  • If hypovolemic shock present, volume expansion with packed RBC (PRBC) transfusion is indicated.

  • Dietary counseling; in iron deficiency anemia and iron supplement.

Aplastic Anemia

Christine A. Schindler


  • Congenital aplastic anemia occurs in approximately 20% of cases.

  • Acquired aplastic anemia occurs in approximately 80% of cases. Acquired aplastic anemia may be a result of exposure to drugs, chemicals, ionizing radiation, or viruses.

Clinical Presentation

  • History: mucosal/gingival bleeding, headaches, fatigue, easy bruising, rash, fever, mucosal ulcerations, or recurrent viral infections.

  • Symptoms: pallor, tachycardia, petechial rash, purpura, ecchymoses, or jaundice.

  • Symptom severity depends on the level of pancytopenia.

Diagnostic Evaluation

  • Decrease in hemoglobin, white blood cell (WBC) count, and platelet count.

  • Reduction in or absence of the absolute number of reticulocytes.

  • Peripheral blood smear; no abnormal cells.

  • Reduction or absence of hematopoietic elements from bone marrow aspirate.


  • Transfusions of RBCs and platelets.

  • Antibiotic therapy.

  • Bone marrow transplantation (BMT).

  • Immunosuppressive therapy if unable to receive a BMT.

Diamond-Blackfan Anemia (Diamond-Blackfan Anemia)

Christine A. Schindler


  • Mutation for Diamond-Blackfan is on chromosome 19, which encodes for a ribosomal protein known as RPS19.

Clinical Presentation

  • Symptoms: pallor, fatigue, irritability, syncope, and dyspnea during feeding.

  • Physical examination: irregular heartbeat, hypotonia, short stature, and evidence of failure to thrive.

  • Associated with physical defects including craniofacial, hands, upper limbs, cardiac, or genitourinary.

Diagnostic Evaluation

  • Profound macrocytic anemia; WBCs and platelet count generally normal.

  • Reticulocytopenia.

  • Increased percentage of hemoglobin F for age.

  • Elevated erythrocyte adenosine deaminase activity.

  • Decreased or absent erythroid precursors in bone marrow aspirate.

  • Genetic screening; Diamond-Blackfan anemia—mutation in RPS19.


  • Corticosteroids, frequent blood transfusion, BMT in some cases.

  • Hematology, BMT, and endocrinology team involvement.

Coagulation Disorders

Disseminated Intravascular Coagulation (DIC)

Sheree H. Allen


  • Acquired condition resulting from single or multiple underlying conditions or disease processes.

  • Associated with significant mortality and may not resolve with treatment of the underlying cause.

  • Infection—most common cause (approximately 35% of all cases).

    • Gram-negative (most commonly associated with DIC) or gram-positive sepsis.

    • Viral processes.

    • Fungal infection.

    • Severe pancreatitis.

  • Trauma; penetrating brain injury, burns, or multiple trauma.

  • Hematologic malignancies; hemolytic processes.

  • Acute respiratory distress syndrome.

  • Obstetrical complication.

  • Necrotizing enterocolitis.

  • Extra Corporeal Membrane Oxygenation.

  • Graft-versus-host disease (GVHD).

Clinical Presentation

  • No predictable pattern. DIC is not a primary disorder, but is always a complication preceded by a significant illness or injury.

  • Symptoms: headache, altered level of consciousness, bleeding, disproportionate bruising.

  • Findings: diffuse bleeding; often initial symptom, petechiae, ecchymosis, purpura, and hematoma, gingival bleeding and epistaxis, hematuria, hematemesis and melena, intrahepatic hemorrhage, signs and symptoms of shock, thrombosis can be present, cool mottled skin, pallor, poor perfusion, tissue necrosis, and gangrene.

  • Multiorgan system failure can occur related to ischemia and/or necrosis, resulting in respiratory insufficiency or failure, renal failure, and altered level of consciousness.

Diagnostic Evaluation

  • Laboratory testing—may change depending on the length of illness; there is not one confirmatory laboratory study to diagnose DIC. The following findings are consistent with DIC:

    • Prolonged PT.

    • Prolonged activated partial thromboblastin time.

    • Increased international normalized ratio (INR).

    • Decreased fibrinogen and platelet count.

    • Schistocytes (fragmented RBCs) on complete blood count (CBC) smear.

    • Elevated fibrin split product (FSP).

    • Positive/elevated D-dimer (marker is sensitive to endogenous generation of thrombin and plasmin).


  • Supportive therapy should target specific organ symptoms affected while maintaining perfusion of vital organs until DIC is controlled.

  • Monitor vital signs, central venous pressure, and oxygen saturation.

  • Administer oxygen as needed; additional respiratory strategies as needed.

  • Antibiotics—organism specific for presumed or identified infectious etiology.

  • Fluid and electrolyte balance; correct acidosis and shock.

  • Administer vitamin K as indicated.

  • Frequent evaluation of laboratory studies—coagulopathy profile, CBC, chemistry, and acid-base balance (arterial or venous blood gases).

  • Blood product administration and replacement.

  • Cryoprecipitate—provides fibrinogen, factor VIII, and vonWillebrand factor.

  • Consider anticoagulation (e.g., heparin); controversial and not widely recommended; inhibits thrombin generation; efficacy has not been demonstrated in clinical trials.

  • Antithrombin III (ATIII)—An a2-globulin that inhibits coagulation.

  • Consider Aprotinin—slows fibrinolysis, but not routinely used.

Hemolytic Uremic Syndrome

Sheree H. Allen


  • Contamination of water, meat, fruits, and vegetables with infectious bacteria; peak incidence during summer.

  • E. coli 0157:H7 is the most common etiology of postdiarrheal (D+) HUS.


  • D+ HUS—Postdiarrheal or typical HUS; occurs in previously healthy children who have had recent gastroenteritis. Mortality rate is 3% to 5%; associated with renal failure in 50% to 70% of patients affected. Bacterial verotoxins, absorbed through intestinal mucosa, are produced by E. coli O157:H7 infection (Shiga toxin; most common cause), Shigella dysenteriae, Citrobacter freundii, and other subtypes of E. coli (also Shiga toxin).

  • DHUS—Atypical or sporadic HUS is less common and more severe than D+HUS with an approximately 25% mortality rate. It is associated with end-stage renal disease in approximately 50% of cases. More common in adulthood, atypical DHUS infection may have a familial link and may also begin in the neonatal period; occurs year round with no gastrointestinal (GI) prodrome. Causative factors include Inherited factor H deficiency (10%-20%); inhibits complement activation, Membrane cofactor protein mutations, Streptococcus pneumoniae infection, medications including Cyclosporine and Tacrolimus.

Clinical Presentation (Typical D+HUS)

  • Previously healthy child with exposure to contaminated source, incubation period 3 to 5 days.

  • Symptoms: abdominal pain; watery, nonbloody diarrhea, fever, weakness, lethargy, irritability.

  • Progression to hemorrhagic colitis occurs 5 to 7 days after onset of diarrhea.

  • Findings: pallor, petechiae, ecchymoses, hematuria, oliguria, azotemia, hypertension; may progress to anuria, hepatomegaly, splenomegaly, hematemesis, edema.

  • Tremor and seizures (approximately 20% of cases).

Diagnostic Evaluation

  • HUS diagnosis is supported by patient history and the presence of microangiopathic hemolytic anemia, thrombocytopenia, and ARF.

  • Reticulocytosis and abnormal RBC morphology.

  • Schistocytes, burr, and helmet cells on smear; fragmented erythrocytes.

  • Anemia; decreased plasma haptoglobin.

  • Thromobocytopenia.

  • Leukocytosis is common.

  • Coagulation profile is often normal.

  • Stool cultures are often positive for E. coli 0157:H7, or other toxin-producing bacteria; however, not always detected.

  • Serum ELISA testing—should be done at diagnosis and repeated 2 weeks later (determines presence of antibodies to Shiga toxin E. coli serotypes).

  • Elevated BUN, serum creatinine, bilirubin, and potassium.

  • Coombs negative.

  • Microscopic hematuria, proteinuria, and casts on urinalysis.


  • Typical D+HUS.

    • Supportive therapy—90% of patients survive the acute phase.

      • Greater than 50% recover full renal function.

      • Antibiotics are not indicated (may stimulate the bacteria to release more toxins that can damage platelets, blood vessels, and kidneys).

      • Dialysis—(approximately 50% of patients).

      • Correct electrolyte imbalances, azotemia, manage fluid overload.

      • Maintain adequate nutrition and caloric intake while observing renal protective diet.

      • Correct anemia—75% of patients require PRBC transfusion.

      • Control hypertension.

      • Oral calcium channel blocker (e.g., nifedipine).

      • Intravenous (IV) calcium channel blocker (e.g., nicardipine) or nitroprusside.

    • Long-term follow-up:

      • Monitor blood pressure (BP) and urinalysis.

      • Complications are uncommon; however, proteinuria, decreased glomerular filtration rate, and hypertension may recur up to 1 year later.

  • Atypical DHUS.

    • Plasmapheresis—consider for patients with factor H deficiency; may limit renal involvement temporarily, but does NOT prevent progression to end-stage renal disease and has not been shown to prevent recurrence of DHUS.

    • Kidney transplantation—8% to 30% if recurrence persists.

    • Long-term follow-up with monitoring of BP and urinalysis.

      • Proteinuria, decreased glomerular filtration rate, and hypertension may recur up to 1 year later.

Hemophagocytic Lymphohistiocytosis

Daniel K. Choi


  • Primary hemophagocytic lymphohistiocytosis (HLH): primarily in newborns and young children.

    • Often associated with a family history of HLH and/or in patients with genetic mutations associated with specific immune cell defects that lead to HLH.

    • Gene defects associated with increased risk of HLH: Perforin (PRF), MUNC (UNC13D), Syntaxin 11 (STX11), and SAP (SH2-D1A).

  • Secondary HLH: Older children, usually secondary to an underlying medical condition with an underlying immune system defect that acts as a “trigger.”

    • Conditions associated with malignancy, autoimmune disease, immune deficiency, and specific infections (e.g., Ebstein-Barr virus, cytomegalovirus [CMV]).

Clinical Presentation

  • Variable presentation; often appear quite ill.

  • Most “common” presentation is prolonged high fever (≥38.5°C), hepatosplenomegaly, hepatitis, and cytopenias (at least two cell lines).

  • Can affect any organ system; notable systems include the skin, pulmonary, and CNS.

  • A high index of suspicion is needed; the diagnosis can often be confused with malignancy, Kawasaki Disease, and severe infection.

Diagnostic Evaluation

  • Criteria first proposed in 1994, and updated in 2004, and are often referred to as the HLH-2004 Criteria:

    • A molecular diagnosis consistent with HLH: pathologic mutations of PRF1, UNC13D, Munc18-2, Rab27a, STX11, SH2D1A, or BIRC4; or

    • Five out of the eight criteria listed below are fulfilled:

      • Fever ≥38.5°C.

      • Splenomegaly.

      • Cytopenias (affecting at least two of three lineages in the peripheral blood):

        • Hemoglobin <9 g/dL (in infants <4 weeks: hemoglobin <10 g/dL).

        • Platelets <100 × 103 cells/mL.

        • Neutrophils <1 × 103 cells/mL.

      • Hypertriglyceridemia (fasting >265 mg/dL) and/or hypofibrinogenemia (<150 mg/dL).

      • Hemophagocytosis in bone marrow or spleen or lymph nodes or liver.

      • Low or absent NK-cell activity.

      • Ferritin >500 ng/mL (usually much higher in HLH).

      • Elevated Soluble CD25 (alpha chain of soluble IL-2 receptor).

      • Important to note that these are suggested criteria, and that a high clinical suspicion and consultation with a pediatric hematologist/oncologist is warranted.


  • Children are often acutely ill, and usually require close pediatric intensive care unit support and monitoring.

  • Therapy is generally initiated even if there are coinciding infections.

  • Human leukocyte antigen (HLA) typing is usually sent early in the treatment course for possible stem cell transplantation.

  • Induction therapy is generally with dexamethasone, etoposide +/- cyclosporine, with treatment weaning over 8 weeks.

  • In patients with genetic/familial predisposition or recurrent/refractory disease, an allogeneic stem cell transplant with a HLA-matched donor is indicated.

    • Risk of recurrence is much higher in this patient population.

    • Caution must be used with a HLA-matched sibling, as they may also have the genetic/familial predisposition to HLH.


Sheree H. Allen


  • Hemophilia A—“Classic hemophilia”— is a deficiency of Factor VII, occurring 1 in 5,000 male births.

    • The most common and severe form; 80% to 85% of all hemophilia.

  • Hemophilia B—“Christmas disease” is a deficiency of Factor IX deficiency.

    • 1 in 30,000 male births.

Clinical Presentation

  • Symptoms: slow, persistent bleeding after minor injury, hematemesis or melena, epistaxis, hematuria, joint pain, swelling, and decreased range of motion due to bleeding into the joints (especially knees, ankles, and elbows), causing hemarthroses, ecchymosis, and subcutaneous hematoma.

    • Uncontrollable bleeding after injury.

      • 30% to 50% of patients experience earliest symptom during and after circumcision.

  • Neonatal considerations include cephalohematoma, subdural, and periosteal bleeding during delivery, and intracranial hemorrhage (up to 2% of infants).

Diagnostic Evaluation

  • Factor assay to determine deficiency.

    • Hemophilia A: factor VIII assay decreased, prolonged PTT, normal platelets.

    • Hemophilia B: factor IX assay decreased, prolonged PTT.

  • Hematocrit may be decreased in presence of excessive bleeding, normal platelet count.

  • PT will be normal, and PTT prolonged >60 seconds.


  • Blood Product Administration: fresh frozen plasma (FFP), Cryoprecipitate, PRBC.

  • Factor Administration.

    • Prompt factor replacement minimizes the morbidity from hemorrhage.

      • Major bleeding—100% factor replacement.

      • Minor bleeding into muscles and joints—50% to 60% factor replacement.

        • Mucocutaneous bleeding—30% to 50% replacement.

    • Factor VIII—(half-life 8-12 hours).

    • Factor IX—(half-life 12-24 hours).

    • 1-deamino-8-D-arginine vasopressin (DDAVP) for mild to moderate hemophilia A.

      • Parenteral DDAVP or Intranasal DDAVP.

    • Patients should be pretreated with 100% recombinant clotting factor concentrate prior to any surgical or invasive procedure.

Immune Thrombocytopenic Purpura

Sheree H. Allen


  • Cause is unknown; may be acute or chronic.

  • Frequently precipitated by a viral illness.

  • Estimated incidence is 4 to 8 cases per 100,000 population per year (United States).

  • Acute ITP is self-limiting in children <12 years of age; resolves within 6 months.

  • Approximately 10% of children will develop chronic ITP.

Clinical Presentation

  • Bruising and petechiae, epistaxis, GI bleeding, hematuria, menorrhagia, spontaneous bleeding from mucous membranes and gingiva.

  • Intracranial bleeding and splenomegaly are possible.

Diagnostic Evaluation

  • Platelet count <100,000; large platelets on smear.

  • PT and PTT (normal), Fibrinogen (normal), Fibrin degradation products (normal).

  • Diagnosis may be confirmed by bone marrow aspiration; normocellular result with elevated megakaryocytes.


  • Acute ITP—goal is to restore the platelet count.

    • Oral corticosteroids; course may be weeks to months.

    • IV gamma globulin (IVIG) OR Anti D immunoglobulin (WinRho-D).

    • Recurrent monitoring of platelet count guides therapy.

    • Avoid NSAIDS and aspirin.

  • Chronic ITP—(ITP lasting longer than 6 months).

    • Regular administration of IVIG or WinRho-D.

    • Splenectomy.

Henoch-Schönlein Purpura

Sheree H. Allen


  • Usually precipitated by an upper respiratory tract infection, medication, or other environmental trigger.

  • Associated with many infectious agents, with most prevalent organism group A streptococcus; approximately 50% of patients with Henoch-Schönlein purpura have antistreptolysin O antibodies.

Clinical Presentation

  • Recent upper respiratory tract infection and prodrome of fever and fatigue.

  • Commonly presents with tetrad of symptoms:

    • Rash: nonpruritic, erythematous papules or wheals that progress to petechiae, and nonblanching, palpable, purpuric lesions >10 mm diameter; found in dependent areas of body that are subject to pressure and extensor surfaces of the extremities. Trunk is usually spared, and lesions fade over 10 to 12 days.

    • Polyarthralgias: pain, swelling, decreased range of motion; Lower extremity joints most frequently involved.

    • “Bowel angina” – diffuse, colicky abdominal pain with me-lena and vomiting; approximately 70% of patients.

    • Renal symptoms with hematuria, proteinuria, and hypertension; approximately 20-60 % of patients weeks to months after initial presentation

      • Mild renal impairment may progress to nephrotic syndrome and ARF.

      • Renal biopsy consistent with focal and proliferative glomerulonephritis.

Diagnostic Evaluation

  • Based on clinical features and presenting symptoms; renal function should be evaluated at baseline.

  • Platelets normal or elevated.

  • BUN and creatinine may be elevated.

  • Normal coagulation studies.

  • Immune antibody panel—Presence of IgA antibodies in the blood, skin, or glomeruli may help to confirm diagnosis.

  • Urinalysis for evaluation of blood and protein.


  • Rest and activity limitations, with symptomatic management of systemic complications, NSAIDS.

  • Oral prednisone; indicated for patients with kidney involvement.

  • Henoch-Schönlein purpura resulting in severe kidney disease may require plasma exchange, high-dose IV immunoglobulin (IVIG), or immunosuppressant agents.

  • Long-term management of hypertension may be required.

Heparin-Induced Thrombocytopenia

Melanie Muller


  • Heparin-induced thrombosis (HIT) occurs in approximately 2% to 3% of pediatric patients who receive heparin.


  • Exposure to heparin.

    • Duration and extent of exposure.

Clinical Presentation

  • Thrombocytopenia; platelets decrease by >50% within the first 4 to 14 days after initiation of heparin.

  • Occasionally, development of thrombosis is the first sign of HIT, more commonly venous thrombosis.

  • In some patients, rapid onset of thrombocytopenia, occurring within minutes to hours after heparin exposure. This usually occurs as a result of heparin exposure in the previous 100 days.

Diagnostic Evaluation

  • Diagnosis is made based on clinical presentation.

  • Serotonin release assay, heparin-induces platelet activation test, and flow cytometric tests to detect platelet microparticle release may be used

  • Evaluating for other etiologies of thrombocytopenia, including cardiopulmonary bypass within the last 48 hours, presence of bacteremia or fungemia, recent chemotherapy administration, and DIC due to other etiologies.


  • If suspected, immediate removal of heparin and low molecular weight heparin from all sources.

  • If ongoing anticoagulation is needed, use vitamin K antagonist or direct thrombin inhibitor.

  • Platelet recovery and disappearance of antibodies can take weeks once heparin is discontinued.

Glucose-6-Phosphate Dehydrogenase Deficiency

Myra Cleary


  • Three forms have been described.

    • Variant 1: G6PD activity is less than 10% of normal, resulting in severe neonatal jaundice or congenital nonspherocytic hemolytic anemia.

    • Variant 2: G6PD activity is typically less than 30% of the normal range, resulting in an asymptomatic steady state. Individuals who carry this mutation are at risk for neonatal jaundice, acute hemolytic anemia, and favism.

    • Variant 3: Enzyme activity is greater than 85% of the normal reference range, resulting in no clinical manifestations. Considered the “wild type” disease.

  • X-linked inherited disease that affects primarily men.

Clinical Presentation

  • Children with G6PD deficiency are clinically and hematologically normal for the majority of their lifetime.

  • Acute exacerbations may occur with the ingestion of fava beans (favism), during the course of an infection, and exposure to oxidative drugs (e.g., antimalarials, sulfa-containing drugs, aspirin, and quinolones).

  • Symptoms: fever, nausea, abdominal pain, diarrhea, and occasionally vomiting within 24 to 48 hours after oxidative challenge.

  • Findings: Dark brown or black discoloration of the urine is present within 6 to 24 hours after exposure (result of hemolysis); jaundice, pallor, tachycardia, hypovolemic shock, and hepatosplenomegaly may develop.

Diagnostic Evaluation

  • Severe anemia with marked variation in the size of the RBCs resulting in an increase in the RBC distribution width. WBC count may be elevated.

  • Large polychromatic cells with spherocytic morphology as well as markedly irregular-shaped cells known as poikilocytes on peripheral blood smear.

  • Increased reticulocyte count; may reach levels as high as 30%.

  • Heinz body stain: As the RBCs circulate through the spleen, Heinz bodies are removed, resulting in classic “bite cells.” Heinz bodies are identified with methyl violet staining and are denatured hemoglobin and a manifestation of the oxidative injury to the hemoglobin.

  • Hemoglobinuria may be present.


  • Blood transfusion is indicated if the child is hemodynamically unstable or the hemoglobin level declines to <7g/dL.

  • If the hemoglobin is <9 g/dL with evidence of persistent brisk hemolysis with hemoglobinuria, blood transfusion may be indicated.

  • Dialysis may be indicated for acute kidney failure.

  • Neonatal jaundice related to G6PD deficiency is managed with observation for mild cases, phototherapy, and hydration for more significant cases, and exchange transfusion may be beneficial for severe cases.


Christine A. Schindler


  • Congenital methemoglobinemia is caused by diminished enzymatic reduction of methemoglobin back to functional hemoglobin. Patients may present with a cyanotic appearance, but may be aysmptomatic.

  • Acquired methemoglobinemia is generally caused from exposure to certain medications or agents that cause an increase in the production of methemoglobin.

    • Substances that have been implicated in the formation of methemoglobin include:

      • Oxidant drugs: Sulfonamide antibiotics, Quinones, Phenacetin, Benzocaine.

      • Domestic and environmental substances: foods containing nitrates or nitrites, well water with nitrates, aniline dyes, naphthalene (mothballs), soap enemas, certain industrial compounds (e.g., nitrobenzenes, nitrous gases, organic amines).

Clinical Presentation

  • Symptoms depend on the concentration of methemoglobin:

    • 10% to 30% methemoglobin—cyanosis only.

    • 30% to 50% methemoglobin—dyspnea, tachycardia, dizziness, fatigue, headache.

    • 50% to 70% methemoglobin—severe lethargy and stupor.

    • >70% methemoglobin—death.

  • Oxygen administration fails to affect the cyanosis.

  • “Chocolate”-appearing blood with laboratory sampling.

Diagnostic Evaluation

  • Patients with methemoglobinemia and cyanosis may have normal oxygen saturation measurements on pulse oximetry.

  • Rapid screening test—A drop of the patient’s blood should be placed on filter paper. After the filter paper is waved in the air for 30 to 60 seconds, normal blood appears bright red, while blood from a patient with methemoglobinemia remains reddish-brown.

  • Spectrophotometric assays—used for confirmation of methemoglobinemia and for determination of the level of methemoglobin.

  • Arterial blood gas with co-oximetry to measure level of methemoglobin.


  • Remove the causative substance.

  • Depends on clinical severity:

    • Mild symptoms—therapy unnecessary.

    • Severe symptoms—treatment is administration of Methylene blue.

    • Failure of methylene blue therapy may be a result of concomitant G6PD deficiency. Ascorbic acid may be of some value, but if severe symptoms persist, exchange transfusion or hyperbaric oxygen may be required.

Sickle Cell Disease

Nneka Okoye


  • There are several different types of SCD ranging in severity, listed below from most to least common.

    • Sickle cell anemia (HbSS)—most common, majority of patients, and most severe form of disease.

    • Sickle hemoglobin C disease (HbSC)—typically milder disease.

    • Sickle β+ thalassemia (HbSβ+Thal)—typically milder disease.

    • Sickle β0 thalassemia (HbSβ0Thal)—typically severe disease.

    • Rare types of SCD—sickle hemoglobin D disease (HbSD), sickle hemoglobin E disease (HbSE), sickle hemoglobin O disease (HbSO). Variable severity.

    • Sickle cell trait (AS)—This is not a type of SCD, but an asymptomatic carrier state affecting 10% of African Americans.

Clinical Presentation

  • Clinical manifestations are widely variable in all forms of SCD, ranging from asymptomatic, mildly affected, to severely affected.

  • See clinical presentation table below (Table 10.1).

TABLE 10.1 Clinical Presentation and Management of Sickle Cell Disease

Clinical Manifestation


Signs and Symptoms




Decreased hemoglobin and hematocrit.

Often asymptomatic, fatigue, pallor, dizziness, jaundice.


Most marked in HbSS and HbSβ Thalassemia.

Vasoocclusive crisis/event

Vascular occlusion by sickled cells causing tissue ischemia.

Wide range of pain.

Common triggers are cold temperatures, hypoxia, dehydration, acidosis.

Pain and tenderness of affected area, painful area may be edematous.

Low-grade fever possible.

Acetaminophen, NSAIDs, opiates, heat, distraction, massage, hydration.

In infants may manifest as dactylitis/hand-foot syndrome.


Functional asplenia can result in: severe bacterial infections, sepsis, meningitis, osteomyelitis.

Fever, pain, malaise, tachycardia, tachypnea, hypotension, lethargy, weakness, anorexia.

Fevers of 101.5°For higher: prompt evaluation, bacterial cultures, empiric parenteral broad-spectrum antibiotics. Penicillin prophylaxis until at least 5 y of age.

Can be life-threatening.

Splenic sequestration

Sickled RBCs pool in spleen, causing splenomegaly, severe anemia, and shock.

Splenomegaly, abdominal pain, lethargy, pallor, hypotension, tachycardia, weakness, irritability.

Consult hematology. Blood transfusion, IV fluids, pain management, serial CBC monitoring, for recurrent episodes splenectomy.

Typically occurs in patients <5y. Can be life-threatening. Chronic splenomegaly may be seen in those with HbSC.

Acute chest syndrome

Occlusion of lung vasculature by sickled cells causing tissue ischemia.

New infiltrate on CXR along with one or more of the following: tachypnea, fever, cough, chest pain, shortness of breath or hypoxia.

Often associated with significant decrease in hemoglobin.

Antibiotics, oxygen, bronchodilators, pain management, blood transfusion, mechanical ventilation support.

Exchange transfusion most often beneficial.

Clinical condition may deteriorate rapidly. Can be life-threatening.

Cerebrovascular accident

Vascular occlusion by sickled cells and/or damage to endothelial cells of blood vessels.

Ischemia of brain tissue and neurological deficits. Strokes may be ischemic or hemorrhagic.

Motor or sensory deficits, cognitive deficits, asymptomatic with silent strokes.

Exchange transfusion, followed by chronic transfusions.

Can be life-threatening.

Aplastic crisis

Severe anemia with reticulocytopenia often caused by viral infections.

Lethargy, pallor, malaise, fever, symptoms of upper respiratory infection.

Pain management, pseudoephedrine, hydration, consult urology for penile aspiration.

Common etiology: Parvovirus B19.

Avascular necrosis

Bone ischemia and necrosis due to a lack of blood supply to area.

Joint pain especially with ambulation, bone collapse may occur in late stages.

Surgical emergency.

Commonly affects hips and shoulders. Seen more frequently in HbSC.


Painful long-lasting erections.

Painful erection.

Pain management, pseudoephedrine, hydration, penile aspiration.


Vascular occlusion of the vessels in the eye.

Visual changes, vitreous hemorrhage, retinal detachment.


Seen more frequently in HbSC.


Hemolysis leads to increased buildup of bilirubin, resulting in gallstones.

Abdominal pain, jaundice.

Consult surgery.

Typically seen in older children and adolescents.

Delayed growth and puberty

Shorter stature and delayed puberty.

Late gonadarche, adrenarche, thelarche, menarche.

Will attain normal height with late adolescent growth.

Diagnostic Evaluation

  • SCD can be identified through newborn screening in all 50 US states.

  • Confirmatory testing is done with hemoglobin electrophoresis.

  • Prenatal diagnosis is available via amniocentesis or chorionic villus sampling.


  • The only cure for sickle cell anemia is BMT.

  • Hydroxyurea is the only disease-modifying medication to treat SCD; increases fetal hemoglobin levels, resulting in decreased incidence of complications.

  • Other supportive care includes:

    • Initiation of penicillin prophylaxis by 2 months of age and continued to at least 5 years of age.

    • Additional vaccines (i.e., pneumococcal and meningococcal) given at age 2 and 5 years of age.

    • Blood transfusions, either simple, exchange, or chronic.


Cathy Haut


  • Most common worldwide genetic disorder.

  • α-Thalassemia is typically seen in Southeast Asia, people of African descent, China, and Middle East. Greater than 50% of some populations carry the α-thalassemia gene.

  • β-Thalassemia is most common in people of Mediterranean descent; 1.7% of the world’s population has α- or β-thalassemia trait.

  • Must inherit defective genes from both parents to have thalassemia major.

  • Thalassemia minor is often found in an asymptomatic carrier.


  • α-Thalassemia major.

  • β-Thalassemia major, also called “Cooley Anemia.”

  • Thalassemia minor.

Clinical Presentation

  • Typical features: chipmunk facies with prominent frontal bossing, delayed pneumatization of the sinuses, marked overgrowth of maxillae.

  • Bones and ribs become “box-like,” premature fusion of epiphyses, and thinning of the cortex of the bone.

  • Findings: hepatomegaly, splenomegaly, enlarged kidneys with dilated renal tubules, dark urine, cardiac abnormalities, and delayed sexual development.

Diagnostic Evaluation

  • Anemia, typically found in the first year of life.

  • Hypochromic, microcytic anemia with decreased MCV, basophilic stippling, presence of Hgb A.

  • May have hyperuricemia.


  • Primary treatment is blood transfusion and folate replacement.

  • BMT from a matched sibling donor is the best chance for cure.

  • Complications include iron overload from transfusions, congestive heart failure, and early death.

Thromboembolytic Disorders

Christine Guelcher


  • Although relatively uncommon in pediatric patients, the incidence of venous thromboembolism is increasing as a result of advances in surgical and medical care for previously fatal illnesses. Thrombotic complications in pediatric patients are often a result of therapies, including central venous catheters.

Etiology/Risk Factors

  • Acquired risk factors: obesity, smoking, cancer, and medications including L-Asparginase and estrogen-based hormones.

  • Increased risk in pregnancy related to elevations of procoagulant factors and relative deficiency of anticoagulant factors.

  • Trauma can lead to vessel damage; can be compounded by venous stasis secondary to bed rest during recovery.

  • Antiphospholipid antibodies.

    • Presence of antiphospholipid antibodies on two occasions (separated by 12 weeks) and a thrombotic event is considered antiphospholipid syndrome.

    • Significantly increased risk for recurrent thrombosis.

    • Consider indefinite anticoagulation to prevent repeated thrombotic events.

  • Inherited risk factors.

    • Factor V Leiden mutation is the most common inherited thrombophilia, affecting 5% of Caucasians; rare in African or Asian populations. Factor V is not cleaved by activated protein C, resulting in resistance to activated protein C.

    • Prothrombin gene mutation is the second-most common inherited thrombophilia, more common in Caucasians, involving point mutation that results in increased levels of prothrombin (factors).

    • Protein S deficiency is rare (0.03%-0.13%).

    • Elevated factor VIII, an acute phase reactant, is increased by stresses to the system (e.g., trauma, surgery).


  • Symptoms: impaired/absent blood flow in a deep vein. DVT in an extremity results in painful swelling of the extremity; symptoms depend on the location of the clot and the impact on blood flow to the distal vessels.

  • VT in the neck vessels can result in superior vena cava syndrome.

  • Pulmonary embolus can be life-threatening; symptoms may be more subtle in pediatric patients.

  • Cerebral sinus venous thrombosis is a thrombus in the deep veins of the head, resulting in persistent headache, blurred vision, neurologic signs, or seizures.

  • Renal vein thrombosis is associated with nephrotic syndrome, presenting with generalized edema.

  • Portal vein thrombosis causes splenomegaly with thrombocytopenia and anemia. Esophageal varices can result.

  • May-Thurner Syndrome is a vascular anomaly in the pelvis in which the right common iliac artery compresses the left common iliac vein; predisposes patients to left lower extremity DVT.

  • Paget-Schroetter syndrome is an upper extremity DVT that results from venous thoracic outlet syndrome, in which the axillary and subclavian veins are compressed at their exit site into the chest. Thrombosis is triggered by repetitive overhead arm motion (e.g., baseball pitching) that exacerbates the compression.

Diagnostic Evaluation

  • Imaging.

    • DVT—Doppler ultrasound can document the presence and extent of most DVTs (CT/MRI evaluate extension into the pelvis or head).

    • Pulmonary embolus—Spiral CT or ventilation-perfusion scan.

    • Cerebral sinus venous thrombosis—Contrast-enhanced MRI scan.

    • Renal vein thrombosis, portal vein thrombosis—Doppler US or Contrast CT scan.

Laboratory Evaluation

  • Evaluate for prothrombotic risk factors.

  • Some laboratory tests (e.g., protein C, protein S, ATIII) may be low with acute thrombosis.

  • Other laboratory tests may be elevated (e.g., factor VIII) with acute thrombosis.

  • Tests should be repeated if abnormal in the acute phase of disease.

  • Anticoagulation monitoring:

    • PTT is an indirect measurement of anticoagulation and should be correlated with patient’s anti-Xa level.

    • Anti-Xa is a more direct measure of heparin anticoagulation.

    • Anti-Xa levels for patients receiving low molecular weight heparin (e.g., Enoxaparin).

    • PT for patients receiving vitamin K antagonist (e.g., warfarin).

FIGURE 10.1 • Coagulation Cascade.


  • The American College of Chest Physicians guidelines (2012) recommend that pediatric patients with a catheter-related thrombotic event undergo removal of a central venous access device within 3 to 5 days of starting anticoagulation. Follow protocols for continued therapy and prophylaxis if catheter is not removed.

  • For pediatric patients who have other risk factors that may resolve, the guidelines suggest anticoagulation treatment for at least 3 months or more with consideration of risk factor resolution (Figure 10.1).

  • Patients with occlusive thrombosis will develop collateral vessels, and some thrombi will never completely resolve. Anticoagulation therapy is designed to prevent propagation of the thrombus as fibrinolysis will occur to break down clot.

Von Willebrand Disease

Christine Guelcher


  • Von Willebrand disease (VWD) was first discussed in 1924 as a bleeding disorder that was associated primarily with mucosal membrane bleeding. Inheritance pattern is autosomal dominant. Affected patients had prolonged bleeding times, but normal clotting times. VWD affects between 0.1% and 1% of the world population.


  • There are three main types of VWD that are characterized by the qualitative or quantitative defects in von Willebrand factor (VWF).

Clinical Presentation

  • Often diagnosed later in life.

  • History of easy bruising, frequent epistaxis (incidence can be 50% to 75%), heavy menstrual bleeding, or bleeding after a surgical/dental procedure.

Diagnostic Evaluation

  • Von Willebrand protein levels may fluctuate, so repeated laboratory testing may be needed for diagnosis.

  • Other screening tests can be used to identify coagulation factors and assist in diagnosis, but studies are complicated and not always reliable.


  • Treatment capitalizes on interactions that occur during times of stress or with hormonal changes.

  • Desmopressin acetate (DDAVP).

    • Stimulates release of VWF and factor VIII.

    • Management of prolonged or refractory bleeding and prior to minor elective procedures.

  • Antifibrinolytic agents.

    • Used in managing recurrent bleeding in VWD, but do not stop active bleeding; slow the breakdown of clots to preventing rebleeding.

  • Aminocaproic acid (Amicar); contraindicated with hematuria.

  • Tranexamic acid (Lysteda): FDA-approved for menorrhagia.

  • VWF concentrates are derived from human blood donation.

  • The von Willebrand containing factors have both von Willebrand antigen and factor VIII.

Transfusion Therapy

Cathy Haut


  • Modern methods of blood transfusions began only in 1901, when blood types were discovered.

  • Pretransfusion typing is performed to determine the best match for minimal complications.


Jan 30, 2021 | Posted by in NURSING | Comments Off on Hematology and Oncology Disorders

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