Week 38: Hematology

This patient with sickle cell disease (SCD) presents with acute chest syndrome requiring broad-spectrum antibioticsand intensive care unit (ICU) admission. SCD is a genetically determined disease due to an abnormal allele for hemoglobin beta chains. The end result of this abnormality is a sickled cell that is less deformable and can cause increased viscosity and sludging of the blood. Additionally, cells are sequestered in the spleen and the liver leading to destruction. Patients experience chronic hemolysis, vaso-occlusive events, thrombosis and ultimately, end organ injury. Splenic autoinfarction occurs early in life and makes patients more susceptible to encapsulated organisms such asStreptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitides. Acute chest syndrome is the leading cause of death in SCD and is defined as fever, chest pain, and the presence of new pulmonary infiltrates. Management consists of supportive care, supplemental oxygen if needed, broad spectrum antibiotics, andadmission to the ICU.

The patient in the question stem is suffering from vasoocculsive crisis, or pain crisis of the bones. In adults, this is the most common in the chest, long bones, and back. The mainstay of treatment is narcotics and IV fluids.

Acute cerebrovascular accident is a complication in sickle cell patients due to intravascular sickling and vasoocclusion. It typically manifests as ischemic changes of large intracranial arteries. However, in older patients, hemorrhagic changes can be seen as arterial walls have been weakened from prior infarcts. The ideal treatment is exchange transfusion; it is the most effective method to reduce the percentage of sickled hemoglobin and to reduce intravascular sickling and vasoocclusion. Exchange transfusion also helps minimize the risk of transfusion-associated circulatory overload and associated pulmonary edema, in addition to reduced risk of stroke recurrence. Unfortunately, there are no published evidence regarding the safety and efficacy of thrombolytics in sickle cell patients with acute ischemic strokes. If exchange transfusion is available, this option should be pursued first.

This patient is likely suffering a vasoocclusive pain episode, triggered by a likely viral upper respiratory infection. The provided information does not suggest any life-threatening complications (acute stroke, acute chest syndrome, acute bacterial infection, aplastic crisis, symptomatic anemia) that would require further blood tests or imaging at this time.

For patients who are hypovolemic, IV normal saline resuscitation would be indicated. However, there is no indication in this patient that he is dehydrated. If pain is not adequately controlled with initial PO/IM, then IV pain medication may be attempted.

Acute chest syndrome is the leading cause of death in adult sickle cell patients. It is a syndrome that includes pneumonia, pulmonary infarction, pulmonary embolism, bone marrow infarction, and fat emboli. To make the diagnosis, patient must have consolidation or infiltrate on CXR, and at least 1 of the following symptoms: fever >38.5°C, chest pain, tachypnea, cough, wheezing, or PaO2 <60mmHg. Treatment includes pain control, fluid hydration, antibiotics to cover for both typical and atypical organisms, and oxygen. Bronchodilators may be used, especially if patients already have underlying reactive airway diseases. Glucocorticoids should be avoided as studies have shown rebound vasoocclusion and pain crises following the cessation of steroids.

Although there is limited evidence regarding transfusion therapy in acute chest syndrome, transfusion is considered a mainstay therapy for acute chest syndrome. Some guidelines suggest simple blood transfusion in mild-moderate acute chest syndrome cases, while recommending exchange transfusion in moderate-severe cases.

Mild acute chest syndrome criteria include: O2Sat >90% on room air; segmental/lobar infiltrates involving no more than 1 lobe on CXR; and response to simple transfusion of no more than 2units RBC.

Moderate acute chest syndrome criteria include: O2Sat at least 85% on room air; segmental/lobar infiltrates involving no more than 2 lobes on CXR; and response to transfusion of 3 or more units RBC.

Severe acute chest syndrome criteria include: respiratory failure requiring mechanical ventilation; O2Sat <85% on room air; segmental/lobar infiltrates involving at least 3 lobes on CXR.

Very severe acute chest syndrome criteria include: presence of ARDS or life-threatening lung failure.

Given the initial transcutaneous oxygen saturation 88% on room air, this patient is classified as moderate acute chest syndrome. Hematology should be consulted for transfusion therapy.

Acute dactylitis is the most common presenting symptom for patients with sickle cell disease. It most common occurs in patients 6-18 months of age, and represents bone infarction. It is not an infection.

The genotype HbSC is associated with a higher level of total hemoglobin and a less-severe course; however, these patients are at greater risk for avascular joint necrosis. In patients with HbS beta thalassemia, the severity of disease is determined by the severity of the thalassemia mutation. Patients with mild HbS beta+ thalassemia will have near-normal lives, whereas the natural history of HbS beta0 thalassemia is similar to HbSS.

This patient is most likely suffering from transfusion-related acute lung injury (TRALI), one of the leading causes of transfusion-related mortality. It is most closely associated with platelet and fresh frozen plasma transfusions, though cases have been reported with packed red blood cells since there is some residual plasma in the packed cells. Symptoms begin abruptly during transfusion or within six hours and resemble adult respiratory distress syndrome with noncardiogenic pulmonary edema, dyspnea, hypoxemia, and bilateral infiltrates on chest radiograph. It is thought to be caused by granulocyte recruitment and degranulation. As with all transfusion-associated complications, the transfusion should be stopped immediately and supportive care instituted. Most cases resolve spontaneously.

ABO incompatibility (A) causes intravascular hemolysis of transfused red blood cells, producing hemoglobinemia and hemoglobinuria. The onset is immediate. Symptoms include fever, chills, headache, nausea, vomiting, a sensation of chest restriction, and severe joint pain. ABO incompatibility is most often due to human error. An allergic transfusion reaction (B) can vary in severity from simple pruritus with urticaria to anaphylaxis with wheezing and bronchospasm. This patient’s respiratory symptoms are not bronchospastic in nature. Although TRALI can be confused with acute transfusion-associated circulatory overload (TACO) (C), TRALI is associated with hypotension, whereas TACO is associated with a rapid rise in blood pressure.

Pancytopenia (a reduction in all blood cell lines: erythrocytes, leukocytes, and platelets) with a low reticulocyte count is suggestive of aplastic anemia. The use of medications known to cause bone marrow suppression further suggests drug-induced aplastic anemia. Bone marrow generates pluripotent stem cells that differentiate into red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Immature red blood cells are called reticulocytes. When red blood cell production is increased, the erythrocyte count becomes elevated. If this level is reduced, concern is raised about the integrity of bone marrow stem cell production. When red blood cell counts are low (anemia), the hormone erythropoietin is released to accelerate red cell production. Aplastic anemia is a rare type of anemia that is caused by drugs or chemicals in 50% of cases. Drugs that suppress bone marrow production include chloramphenicol, anticonvulsants (e.g., carbamazepine), insecticides, sulfonamides, and gold. Medical conditions associated with aplastic anemia include viral hepatitis, radiation, pregnancy, and autoimmune diseases. Aplasia may affect a single cell line (e.g., pure red cell aplasia) or all cell lines. Symptoms of aplastic anemia may include fatigue, malaise, infection (from neutropenia), or mucosal bleeding (from thrombocytopenia). Bone marrow analysis is needed for definitive diagnosis.

Disseminated bacteremia (A) with certain organisms (e.g., Streptococcus pneumoniae, Neisseria gonorrhoeae) may present with purpura or petechiae. However, these patients are septic with fever, hypotension, lactic acidosis, and usually normal or elevated white blood cell counts and normal red blood cell counts. Disseminated intravascular coagulation (B) is a consumptive coagulopathy with multiple etiologies (e.g., sepsis, trauma, pregnancy, cancer) that can also present with excessive bleeding and petechiae. Thrombocytopenia and schistocytes are characteristic, as well as abnormal coagulation tests. Red blood cell and white blood cell lines are typically unaffected. A type I hypersensitivity reaction (D) is an immunoglobulin E (IgE)-mediated process that results in a massive, abrupt immune response affecting multiple organ systems (e.g., skin, respiratory, circulatory). Anaphylaxis is an example.