Hematologic Disorders - EMBR 2nd Edition

Educational Objectives

The Audio-Digest Emergency Medicine Board Review — Second Edition

The lecture you’ve selected is part of the Audio Digest Emergency Board Review Course. Our overall Board Review Course is designed to match the defined learning objectives of the American Board of Emergency Medicine, and it is intended to provide a source of review material for those who are preparing for the ABEM's Continuous Certification Examination and for those preparing for the ABEM’s Initial Certification Examination. The goal is to provide a comprehensive update in many aspects of emergency medicine practice that will enhance the lifelong learning experience.

Course Objectives

Upon completing this educational activity, participants will be able to:

1. Rapidly diagnose and medically respond to a wide variety of critical issues presenting in the emergency department.
2. Triage the need for medical care (as appropriate) and initiate therapeutic procedures where needed.
3. Manage patients who require continuing respiratory and cardiovascular support until stable or transitioned to other hospital care centers.
4. Determine circumstances in which hospital care beyond the emergency department is required, and initiate procedures to obtain such care.
5. Prescribe drugs as appropriate for the short term management of presenting medical problems.

After listening to this lecture and reading the accompanying summary, the clinician will be better able to:

1. Discuss the pathophysiology and diagnosis of hematologic disorders.
2. Recognize the indications for transfusion and identify complications related to transfusion therapy.

Summary

Transfusion: virtually the only procedure done in emergency medicine relating to hematology; need to know the indications for transfusion, the intervention, how to perform the procedure, and the possible complications and treatment for them; “blood transfusion” refers to the transfusion of specific blood products (eg, packed red blood cells [RBCs], administered to raise the hemoglobin level); the level at which transfusion is indicated varies depending on diagnosis, which blood products are being administered, past medical history and comorbidities of the patient, rapidity with which hemoglobin was lost, and whether or not the patient is symptomatic; one unit of packed RBCs constitutes 250 mL; it is not for volume replacement; hemorrhaging patients requiring volume replacement should receive packed RBCs for the replacement of hemoglobin and warmed crystalloid for the replacement of volume; crystalloid should not necessarily be given to trauma patients requiring resuscitation; trauma patients who require volume replacement should receive prompt administration of packed RBCs as well as judicious crystalloid administration; increasing hemoglobin level improves oxygen delivery, which is essential for the trauma patient and the anemic patient; judicious crystalloid administration is important when volume is needed bearing in mind the principles of permissive hypotension and trauma

Packed RBCs: 1 unit of packed RBCs raises the hemoglobin by approximately 1 point unless bleeding continues; the customary starting order is 2 units; exsanguination of patients requires treatment with universal donor blood type O negative to avoid continued decompensation while waiting for cross-matched blood; patients who have had prior transfusion reactions or immunocompromised patients can receive cells that have been pretreated by washing or irradiation for leukocyte reduction

Fresh frozen plasma (FFP): contains all of the coagulation factors but no platelets; the first intervention for bleeding patients with an undiagnosed bleeding disorder; indicated in the patient on warfarin therapy who is actively bleeding or is admitted for emergency surgery; standard starting dose is 4 units; clinician must cross-match for FFP transfusion; FFP carries a risk for transmission of infectious disease

Platelets: appropriate for bleeding patients who have thrombocytopenia or inadequate or dysfunctional platelets; typical platelet pack is 6 units, which raises the platelet count by 50,000 mL; cross-matching for platelets is preferred if time and clinical condition permit but is not necessary; there is a risk for transmission of infection

Cryoprecipitate: transfusions contain substantial quantities of factor VIII, von Willebrand factor (VWF), and factor I (ie, fibrinogen); effective in the treatment of congenital and acquired hypofibrinogenemia; not first-line treatment but can be used to treat bleeding attributable to VWF or hemophilia A; cross-matching is not necessary; carries a risk for hepatitis and of transmission of HIV; physicians must assess the risk-benefit ratio

Factor concentrates: first-line treatment for factor deficiencies when available; do not contain fibrinogen but provide high concentrations of the specific factor that the patient needs in a relatively small volume; first-line treatment in cases of symptomatic hemophilia and VWF; patients with hemophilia A are factor VIII deficient; patients with hemophilia B are factor IX deficient; patients who require replacement of VWF are transfused with factor VIII concentrate; current factor concentrates are considered free of risk of transmission of hepatitis and for HIV virus

Transfusion method: blood products are infused intravenously with warm hypotonic solutions devoid of calcium or glucose; normal saline is a good choice; cross-matching for packed RBCs and FFP is required; matched platelets are desirable; when immediate transfusion is mandated or a rare blood type is not available, type O negative blood may be administered

Autotransfusion: frequently used in cases of hemothorax; employs a special autotransfusion kit; blood exiting the thoracic cavity through a chest tube passes through a filter and is then transfused back into the patient; mitigates the need for massive transfusion in many patients; autotransfused blood collected from the thoracic cavity does not, however, contain normally functioning platelets and the levels of fibrinogen are decreased; autotransfusion is acceptable to many Jehovah’s Witnesses, avoiding the ethical dilemma for both patient and doctor when transfusion is necessary

Complications: transfusion reactions can be immediate or delayed

Febrile response: most common, least dangerous, immediate reaction; patients generally experience fever, chills, and fatigue, and rarely progress to the more serious symptoms of hypotension and respiratory distress; there are no specific signs or symptoms that predict reaction to transfusion; carefully monitor any patient who becomes febrile following a transfusion

Allergic reactions: true allergic reactions are rare but dangerous; not unlike other allergic reactions characterized by urticaria and possible progression to laryngeal edema and shock; patients should be treated with diphenhydramine, steroids, and an H2-blocker and given supportive care; patients with laryngeal edema should be intubated if there is not a prompt response to pharmacologic therapy

Delayed complications: transmission of bloodborne viruses and malaria; hepatitis C is the most common organism transmitted by banked blood; Epstein-Barr virus, cytomegalovirus, T-cell lymphotropic virus, other hepatitis viruses, and HIV (rare) can be transmitted; extravascular hemolysis — a delayed complication appearing 1 to 2 weeks after transfusion (underscores the importance of good history taking in the emergency department[ED]); question patients who present with weakness, dizziness, and fatigue with an unexplained low hemoglobin level about their transfusion history; extravascular hemolysis may be the diagnosis; massive transfusion (defined as the transfusion of at least 50% of full body blood volume over 12 to 14 hours) can often result in diminished delivery of oxygen to the tissues or coagulopathies; at rest, oxygen delivery is equal to 4 times oxygen consumption, allowing for a wide margin of safety as the body operates with a large oxygen reserve; when intravascular volume is normal and the patient has a normal ejection fraction and adequate cardiac output, oxygen delivery is adequate and the patient should be completely asymptomatic until the hematocrit is equal to or below 10%; the body can tolerate a surprisingly low hemoglobin and hematocrit if there is no volume depletion and cardiac function is optimal; with transfused blood, release of oxygen is impaired; banking of blood reduces the 2, 3-bisphosphoglycerate (BPG) level, shifting the oxygen-hemoglobin dissociation curve to the left; transfusion of only a few units should not present a clinical problem because even transfused RBCs will regenerate 2,3-BPG to normal levels within 24 hours; continuous transfusion over a 24-hour period is likely to result in hypoxia at the cellular level

Coagulopathy after massive transfusion: a multicellular and multifactorial event; fluid replacement therapy and dilution of clotting factors have led to the doctrines of permissive hypotension, damage-control resuscitation, and prompt surgical intervention; most emergency physicians and trauma surgeons administer FFP as part of a massive transfusion protocol or to patients who are bleeding and in shock but not prophylactically; platelets should also be administered as part of a massive transfusion protocol; defects in coagulation can develop very rapidly in the trauma patient leading to disseminated intravascular coagulation (DIC); patients requiring massive transfusion are frequently given cold blood simply because warmed product is not available; this, combined with the bodily exposure that is part of trauma examination and stabilization, can result in significant hypothermia for the patient, resulting in decreased cardiac output and increased cardiac irritability; microembolization of degradation products of platelets and fibrin is also more common with refrigerated blood; aggregates are associated with the development of adult respiratory distress syndrome; micropore filters should be changed frequently; citrates that are used to preserve blood chelate ionized calcium; although there is no indication for prophylaxis, patients undergoing massive transfusion should receive calcium supplementation if there is evidence of myocardial impairment; acidosis and hyperkalemia are also consequences; blood chemistry should be checked routinely

Laboratory tests

Cutaneous B-Cell Lymphoma: when evaluating a patient with abnormal bleeding, a complete blood count (CBC) is routinely ordered in the ED

Platelet count: important information in the patient with undifferentiated abnormal bleeding; normal platelet range is 150,000 to 400,000/mm²; bleeding with minor trauma will occur with counts below 50,000/mm²; spontaneous hemorrhage can occur with counts below 10,000; consider the reason for the decrease in platelet count; platelet production may be impaired; platelet production may be normal but platelets are being sequestered or destroyed; platelet count reported on the CBC tells you nothing about platelet function, just about platelet number; bleeding disorders that are characterized by low platelet count are types of thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT), and hemolytic uremic syndrome (HUS); heparin and other drugs can also cause abnormal platelet counts, as can some acute disorders such as disseminated intravascular coagulation (DIC) and sepsis or some chronic conditions such as HIV and aplastic anemia; one-half of the patients seen with an unexplained low platelet count have an occult malignancy; include a cancer work-up if the end of the differential diagnosis is reached without finding a cause

Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR): the coagulation panel should be routine when assessing patients with undifferentiated bleeding but is no longer obtained with routine laboratory results; PT — is a measure of the function of the extrinsic or tissue factor pathway primarily reflecting the status of factor VII and the common pathway (eg, factors X, V, II, and I); normal PT values are 10 to 12 seconds; warfarin has its effect on this pathway; PTT — used to assess the intrinsic or contact activation pathway; essentially reflects the status of all factors except factor VII and factor XIII; heparin activity is reflected here; an elevation of both the PT and the PTT can be seen with overdoses of heparin and warfarin, liver disease and vitamin K deficiency, DIC or deficiencies, and abnormal functioning of fibrinogen (factor I); INR -the ratio established by the World Health Organization allowing for uniform assessment of coagulation status through a standardized ratio of the PT to standardized PTT; normal INR is 1; INR of 2 to 3 is considered therapeutic for patients on warfarin therapy; thrombin time — a test that is not done in the ED; measures of the function of factor I in the formation of fibrin clot in patients in the ICU being evaluated for DIC, or with patients who have severe liver disease or myeloma

Coagulation disorders: hemostasis is the maintenance of the balance between clot formation and clot breakdown; it depends upon vascular integrity, adequate function of platelets, coagulation factors, and fibrinolysis; disorders of coagulation may be inherited or acquired; the most common inherited disorders are VWF and hemophilia A; the most common acquired disorders are drug induced (commonly by warfarin); nearly 10% of Americans over the age of 65 are on warfarin therapy

Coagulation cascade: composed of 2 separate pathways; intrinsic pathway — the contact activation pathway; defects result in an elevation of PTT; extrinsic pathway — the tissue factor pathway; defects result in an elevation of PT; pathways conjoin to form the common pathway and function together to produce thrombin; a diagram and explanation of the cascade should be reviewed by candidates preparing for certification and recertification examinations; extrinsic or tissue factor pathway — tissue factor, which is inherent in smooth muscle, pericytes, and fibroblasts, binds to factor VII to form activated factor VII, which catalyzes the conversion of latent factors IX and X to activated factors IX and X; intrinsic or contact activation pathway — begins with kininogen and pre-Kallikrein activating factor XII, which triggers the conversion of X to Xa and the start of the common pathway; prothrombin is converted to thrombin, which catalyzes the conversion of fibrinogen to fibrin; any defect along the cascade can lead to a coagulation disorder

Hemophilia: X-linked recessive disorder, although almost one-half of the cases are actually the result of spontaneous mutation; clinically the hemophilias present an identical picture; hemophilia A (classic hemophilia) — more common and involves factor VIII; hemophilia B (Christmas disease) — involves factor IX

Mild disease: plasma coagulation factor concentrations of 6% to 30% of normal; usually bleed only with trauma or surgery; will present in adolescents or even early adults with a history of heavy bleeding after tooth extraction or a minor traumatic injury

Moderate disease: plasma coagulation factor concentrations of 2% to 6% of normal

Severe disease: concentrations of 1% or less; patients have as many as 30 spontaneous bleeding episodes annually; hemarthrosis is common

Recombinant factors: patients are treated based on bleeding or prophylactically for surgical procedures without risk of transmission of viral disease; exception for heat-treated factor VIII concentrate, which still carries a risk of parvovirus and hepatitis A; factor concentrate is the treatment of choice for patients with moderate to severe disease; plasma half-life of factor IX is almost twice that of factor VIII; dosing for patients with hemophilia B is not as frequent

Mild bleeding event: patients can be transfused to a factor concentration of 30% of normal; typically achieved by transfusion of 20 to 30 U/kg

Moderate bleeding episode: includes hemarthrosis, dental extraction, and minor surgery; desired concentration is 50% of normal and is achieved by transfusion of 25 to 50 U/kg

Life-threatening hemorrhage: requires replacement to 80% of normal with 50 to 80 U/kg; the goal is to halt bleeding; if patient has been to the hospital before with bleeding episodes, he or she might also be able to tell clinician what works; a unit of factor will increase the plasma factor level by 2%; if a patient with hemophilia has a bleeding emergency, their plasma concentration should be assumed to be 0 until proven otherwise

Desmopressin (eg, DDAVP): effective in treating patients with a mild form of hemophilia; dose is 0.3 mcg/kg

Cryoprecipitate: carries a risk for infection with HIV and hepatitis, as well as a risk for allergic and anaphylactic reactions; one bag contains about 100 units of factor VIII; there is no reason to use cryoprecipitate when safe alternatives are available

Prothrombin complex concentrates (PCC): contains factors II, VII, IX and X; can use it to treat factor IX deficient patient; ineffective in hemophilia A, which is a factor VIII deficiency; mildly thrombogenic and can transmit hepatitis virus

Laboratory studies: a CBC is not helpful in diagnosing these patients; hemophilia is a disorder of coagulation, so the platelet count will be normal and any platelet function tests used if the patient comes in with considerable bleeding are normal as well; PTT is elevated because these are disorders of the intrinsic or contact activation pathway; fibrinogen levels are normal

Von Willebrand factor: VWF promotes platelet adhesion so it is classified as a platelet-mediated disorder; an autosomal dominant disorder although occasionally a recessive gene expresses; affects men and women equally; is seen in mild, moderate, and severe forms but in general the clinical presentations are much milder than those seen in hemophilia; many more patients present later in life complaining of hemorrhage, bleeding gums with vigorous brushing of the teeth, episodes of epistaxis, or mild lower gastrointestinal (GI) bleeding

Laboratory evaluation: patients have a normal platelet count; platelet function test is abnormal; PT is abnormal because VWF protects factor VIII; sometimes elevated PTT with VWF

Treatment: desmopressin is first-line treatment for mild to moderate disease; it works effectively and carries no risk for transmission of infectious disease; patients with moderate to severe disease are treated with factor VIII, which is rich in VWF; cryoprecipitate and FFP are effective but the former carries an infectious disease list and the latter is not really a viable treatment considering the substantial volume of transfusion necessary to result in a therapeutic effect

Acquired coagulation defects: defects of secondary hemostasis; the result of inappropriately dosed drug therapy with heparin, warfarin, and low-molecular weight heparin (LMWH); rat poison contains warfarin as its active ingredient; poisoning and suicide-by-overdose patients may fit the coagulation profile of inappropriately dosed warfarin, a normal platelet count, elevated PT, and normal to elevated PTT; heparin overdose is characterized by elevation of the PTT; overdose of LMWH results occasionally in an elevated PTT, but usually that level is normal

Disseminated intravascular coagulation (DIC): life-threatening because of loss of platelets and coagulation factors; RBC destruction, fibrinolysis, and fibrin deposition resulting in small vessel occlusion; patients exhibit uncontrollable bleeding from all body orificesand from visceral and mucosal surfaces and often exhibit pregangrenous changes in the distal peripheral tissues (eg, fingers, toes, nose, and genitals)

Clinical triad: purpura, bleeding, and organ failure

Laboratory triad: decreased platelets and fibrinogen with increased PT/PTT

Treatment: directed at the underlying cause (eg, trauma, burns, sepsis, and cancer); occasionally an unusual cause such as snake bite, heat stroke, or intrauterine fetal demise must be considered; when bleeding is the principal clinical feature, treat with product, such as FFP, platelets, and cryoprecipitate to restore factors; if thrombosis is the principal feature, heparin and antithrombin 3 are the indicated therapies; prognosis is poor and survival percentages differ on the basis of the precipitating diagnosis and how early treatment was begun

Platelet disorders

Thrombocytopenia: the most common platelet disorder, caused by either decreased production of platelets or increased destruction of platelets; decreased production can be secondary to malignancy, aplastic anemia, radiation therapy, follate deficiency, some viral infections, and drugs (eg, thiazides, ethanol, and many chemotherapy medications); increased destruction may be autoimmune disease, as with idiopathic thrombocytopenic purpura, or viral induced, as with HIV, mumps, Epstein-Barr virus, or chickenpox; seen with collagen vascular disease, HELLP syndrome (in pregnant women), HUS, transfusion reactions (discussed earlier), and certain drugs (eg, aspirin, heparin, digoxin, furosemide, the penicillin antibiotics, or sulfonamides)

Idiopathic thrombocytopenic purpura: the most common hemorrhagic disease of childhood; children ages 2 to 6 generally present following an acute viral infection; spontaneous recovery usually in weeks to months (6 months is usually the maximum); diagnosis is often made based on a good history and physical, and treatment is usually supportive; indications for platelet transfusion are severe or intractable bleeding, or a count below 10,000 or 20,000/mm² without bleeding; prednisone is often employed as a treatment modality with recent studies demonstrating efficacy for high-dose dexamethasone as the initial treatment; intravenous immunoglobulin is reserved for children whose platelet counts remain profoundly low after a course of steroids

Thrombotic thrombocytopenic purpura: more common in women and associated with infections, autoimmune disease, pregnancy, and immunosuppressive therapy; microthrombi deposit in the small vessels; a high mortality rate if not diagnosed and treated early

Mnemonic: FAT RN; fever, anemia with schistocytes on the peripheral smear, thrombocytopenia, renal abnormalities (although more common with HUS), and neurologic impairments

Diagnosis: predicated upon the presence of microangiopathic hemolytic anemia causing schistocytes on the peripheral smear; no other criteria are needed; 67% of patients present with neurologic symptoms

Laboratory markers: elevated LDH and decreased haptoglobin

Treatment: plasma exchange transfusion (PLEX) is the key to reducing mortality; FFP should be given if PLEX cannot be started within a reasonable time frame; platelet transfusion should not be attempted even though low platelets characterize this disorder; patients should receive methylprednisolone and undergo dialysis if renal failure is present

Heparin-induced thrombocytopenia (HIT): can develop with the smallest exposure to heparin such as occurs with heparin flushes to an IV port; generally occurs 5 to 10 days after exposure but can occur in patients who have had years of ongoing heparin exposure, as with chronic dialysis; patients are far more likely to be affected a second time than the rest of the population is to experience a first episode; females are affected more often than males and for reasons that are not well understood; patients after surgery are more likely to be affected than medical patients; key to diagnosis is good history taking for things that the patient might fail to mention; disorder results when an IgG antibody to heparin-bound platelet factor IV precipitates; platelet counts are usually decreased by one-half and the thrombotic complexes can result in deep vein thrombosis (DVT), pulmonary embolus, limb necrosis and gangrene, and skin necrosis at the injection site; a high level of suspicion is necessary; clinical picture can sometimes seem contradictory (eg, if a patient has been therapeutic on heparin, is on low molecular weight heparin and develops a DVT, check the platelet count and consider this diagnosis); stop the offending agent (including warfarin), because it decreases protein C levels, and in the presence of the HIT antibodies cases it causes a prothrombotic response; warfarin can be stopped with the administration of 10 mg of vitamin K per os; aggressive interventions are not necessary and transfusion of platelets should be strictly avoided; patients need to be on anticoagulation therapy; start a factor IIA inhibitor (eg, argatroban or bivalarudin)

Disorders of the RBCs

Anemia: absolute reduction in hemoglobin; according to World Health Organization standards, is present when the hemoglobin is ≤13 g/dL in men or 12 g/dL in women; more common in the United States among women, the elderly, blacks, and individuals of lower socioeconomic status; can be attributable to decreased production, increased destruction, or loss of RBCs

Microcytic anemia: main corpuscular volume (MCV) <80 fL

Normocytic anemia: MCV = 80 to 100 fL

Macrocytic anemia: MCV > 100 fL

Hyperproliferative microcytic anemia: attributable to iron deficiency and characterized by thrombocytosis and an elevated red cell distribution width (RDW); can be due to thalassemia, a hereditary disorder, or a chronic disease (eg, cancer, diabetes, thyroid disease, or cirrhosis), in which case the RBC count and RDW may be elevated or normal

Normocytic anemia: can be the result of chronic disease, but most often is acute and attributable to bleeding; hemolysis causes normocytic anemia, and the RDW is elevated or normal

Nutritional anemia or anemia attributable to primary bone marrow disease: cells are normocytic but RDW is elevated; macrocytic anemia with a normal RDW is seen in chronic alcohol use, liver disease, hypothyroidism, and hemolysis; macrocytic anemia with elevated RDW is seen in some nutritional or bone marrow disorders and with certain drug-induced anemias

Acute anemia attributable to blood loss: indications for transfusion have been reviewed

Chronic anemia: presentation is more subtle; patient often comes in with the chief complaint of being weak and dizzy; may complain of fatigue, shortness of breath, dyspnea on exertion, headaches, vertigo, or irritability; a thorough history is essential in directing the physical and laboratory examinations; chronic diabetes results in decreased renal production of erythropoietin; many medications, alternative therapies, and herbal remedies induce anemia; fad diets, generalized poor nutrition, a history of alcohol abuse or a family history of anemia are often contributing factors; may be employment history with exposure to bone marrow toxins, (eg, lead); in children, exposure to lead paint or other contaminants should be elicited; parents of anemic pediatric patients sometimes report a history of pica, which is also seen in pregnant women

Physical examination: start with vital signs; tachycardia and tachypnea, wide pulse pressures, and orthostatic hypotension are signs that treatment is indicated for chronic anemia; skin should be examined for pallor; examination of the palmar creases, conjunctiva, and oral mucosa can make the assessment easier; systolic murmurs and pulmonary rales are often discovered on chest examination; abdominal examination might be significant for hepatomegaly, splenomegaly, or even ascites; check the abdomen for masses because occult malignancy is a common cause of anemia in adults; every patient suspected of having anemia must have a fecal occult blood test; women who have not had routine gynecologic care should have a pelvic examination to rule out malignancies and other sources of bleeding; mental status changes, peripheral neuropathy, and neuritis can be seen in anemic patients

Laboratory workup: a CBC is the most important and most revealing examination; type and cross should also be obtained; a hemoglobin of 8 is generally a threshold for transfusion, but many patients can tolerate far lower hemoglobin levels when chronic disease develops slowly and underlying cardiac function is good; other patients become symptomatic and require transfusion at slightly higher levels; treat the patient, not the numbers, in this case; unconjugated bilirubin level and LDH can be helpful in classifying anemia; elevations in these values occur with hemolytic anemia; urine is positive for blood and urobilinogen levels; chest x-ray is indicated for patients with pulmonary or cardiac findings on examination; cardiomegaly is not uncommon; ECG should be performed on anemic patients who are elderly or those with a history of coronary disease, or those who are symptomatic; a nasogastric tube might be indicated to ascertain upper GI bleeding; abdominal computed tomography (CT) can be used to assess for suspected malignancy

Sickle cell disease: disease is so named because of the shape of the RBCs that result when an abnormal hemoglobin molecule (hemoglobin S) is inherited in place of the normal hemoglobin A; 2 forms of the disease are the heterozygous hemoglobin AS form, (“sickle cell trait”), and the homozygous hemoglobin SS form, or sickle cell disease; more commonly seen in individuals with African ancestry; abnormally shaped cells hemolyze more easily than normal cells; patients are more prone to infection; cells do not tumble freely through the lumens of the smaller vessels, and infarction and ischemia can result; in heterozygous patients less than 50% of RBCs are sickled, so the manifestations are more commonly small, spontaneous bleeds such as epistaxis, hyphema, and hematuria, although vaso-occlusive crisis does occur; patients with heterozygous disease can die from a vaso-occlusive crisis; for the homozygous patient, 75% to 90% of the cells are sickled, and so patients suffer from often unexplained and very severe bone pain; salmonella osteomyelitis, splenic infarction, cholelithiasis and cholecystitis, severe hemolytic anemias, dactylitis, meningitis, and pneumonia secondary to encapsulated organisms, specifically Haemophilus influenza and Streptococcus pneumoniae

Dactylitis: painful swelling of the fingers and toes is often the initial presenting symptom in infants and children and most homozygous patients have had cholecystectomy and sometimes even splenectomy by young adulthood

Crisis: several forms of crisis are observed in patients having sickle cell disease; vaso-occlusive crisis — the most common crisis; patients experience unremitting pain in the thorax or long bones; often they have tried oral narcotic analgesia prior to coming to the ED; treatment includes adequate analgesia, folic acid, and hydration; many hematologists give oral hydration when IV access is difficult; severely affected patients may get a port after years of frequent crises; order a CBC test to look for sequestration or aplastic crisis, test for reticulocyte count, and examine the patient carefully for indications of infection; include a urinalysis or chest x-ray if indicated by history or physical examination; sequestration crisis — commonly seen in the younger pediatric population; signs and symptoms include abdominal pain and pallor and can progress to shock; children often have splenomegaly; hemoglobin levels can drop drastically and often pancytopenia develops; may need to consult a pediatric surgeon for prompt splenectomy; aplastic crisis — usually follows a recent infection (human parvovirus is a common offender); patients present with pallor and lethargy and can progress to frank shock; low hemoglobin count occurs within the context of a low reticulocyte count demonstrating bone marrow suppression; cultures are mandated because of the association with infection; patients frequently require transfusion; remember the role of supplemental oxygen when treating patients in crisis; hemolytic crisis — patient sappear quite ill and jaundiced; patients may progress to shock and transfusion may be required; support shock with IV fluids and seek a source for the infection; infection is the most common cause of death in patients having sickle cell disease; start broad-spectrum antibiotics promptly if signs of bacterial infection are present; acute chest syndrome — cough, fever, chest pain, and shortness of breath; can be seen in any age group; infection and pulmonary infarction contribute to the clinical picture; supplemental oxygen, hydration, and antibiotics are the mainstays of therapy; priapism — male patients with sickle cell disease are prone to priapism, which is treated with terbutaline 0.25 to 0.5 mg administered subcutaneously; if treatment is unsuccessful, a prompt genitourinary (GU) consultation is necessary; transfusion or hyperbaric oxygen therapy are sometimes indicated; patients with sickle cell disease are more prone to infectious arthropathies, meningitis, pneumonia, cerebrovascular accidents, renal papillary necrosis, renal insufficiency, congestive heart failure, low extremity ulcers, retinal detachments, and vascular necrosis

Polycythemia: discovered by Sir William Osler; named with the Greek word meaning “many cells in the blood”; a myeloproliferative clonal stem cell disease, which can be congenital or acquired; patients present with weakness, dizziness, vertigo, tinnitus, visual disturbances, intermittent claudication, and angina attributable to the sludging of hyperviscous blood; history reveals a VWF-type picture with menorrhagia and gingival bleeding, and perhaps mild lower-GI bleeding, especially in patients on aspirin therapy; patients with polycythemia are more likely to have a history of dyspepsia or upper-GI ulcers; vital signs often include elevated blood pressure, and physical examination may be significant for splenomegaly and/or hepatomegaly and a ruddy color to the face, hands, nail beds, and mucosa (ie, plethora)

Diagnosis: clinical but supported by a decreased partial pressure of oxygen, an elevated hemoglobin and hematocrit, and expansion of RBC mass

Treatment: phlebotomy, which should be performed in consultation with the hematologist; antihistamines, androgens, phototherapy, and even splenectomy may be necessary treatments following admission

White blood cell (WBC) disorders: National Cancer Institute estimates that almost 1 million people in the United States are living with hematologic malignancies; for adults, non-Hodgkin lymphoma and chronic lymphocytic leukemia are the most common; lymphoid leukemias predominate in children; normal WBC counts are 4.3 to 10.8 X 10⁹/L; neutrophils represent one-half to two-thirds of WBCs with band presence indicating infection; lymphocytes compose one-quarter to one-half of the cells, monocytes about 10%, and eosinophils and basophils up to 10% combined; disorders of WBCs are the result of overproduction of cells, underproduction, or dysfunction

Leukopenia: refers to a WBCcount less than 1.5 X 10⁹/L, a nonspecific but specific finding; underproduction of WBCs can be secondary to many chemotherapeutic agents, phenytoin, penicillin antibiotics, or sulfa drugs; can also be seen in asplenic anemia and in some forms of leukemia or deficiency of vitamin B12 or folate

Neutropenia: specifically seen with many viruses that used to be typical childhood diseases and also with hepatitis, HIV, Dengue, and yellow fever; caused by bacteria responsible for tuberculosis, rickettsial diseases, salmonella, and tularemia

Leukocytosis: refers to an elevation in the total number of WBCs in circulation more than 2 standard deviations above the age-adjusted mean; does not describe the functionality of those cells; generally secondary to bacterial infection or stress; bacterial infection accounts for almost two-thirds of cases of elevated WBC counts

Lymphocytosis: caused by pertussis, hepatitis, mononucleosis, toxoplasmosis, and cytomegalovirus, or from chronic infections with tuberculosis, syphilis, or Rickettsial diseases

Eosinophilia: typically present in parasitic infection but also seen with protozoa and fungus; overproduction of WBCscan be response to corticosteroids, heparin, lithium, adrenergic agents, granulocyte macrophage colony-stimulating factor, acetylcholine, or to ion poisonings; neoplastic diseases (eg, many of the leukemias and non-Hodgkin lymphoma or cancers with bone metastasis) can cause elevation of WBC count; dysfunction of the WBCs is seen with an increased splenic sequestration that results from cirrhosis or Gaucher disease, from the impaired polymorphonuclear neutrophil function that is seen in chronic diabetes, or from the impaired polymorphonuclear leukocyte and lymphocyte function that is seen in chronic renal failure; use of corticosteroids can also result in WBC dysfunction

Acute myelogenous leukemia (AML): presents with fever, malaise, and symptoms of a general viral syndrome; patients complain of chest pain and shortness of breath and are pallid because of anemia; patients report bleeding (from thrombocytopenia); one-third of the patients have an infection at the time of diagnosis and one-third have splenomegaly on examination; many exhibit gingival hyperplasia; lymphadenopathy is rare; long bones will often be tender to palpation, attributable to the expansion of the intramedullary space; AML is the most common leukemia to present with a rash; raised, nontender nodules are often seen; many AML patients report a history of Sweet syndrome (characterized by the presence of tender, erythematous, vesicular appearing plaques) in the months preceding the diagnosis of AML

Chronic lymphocytic leukemia (CLL): generally presents with lymphadenopathy (an important distinction between AML and CLL); patients report weakness, fatigue, lethargy, exercise intolerance, weight loss, and decreased appetite similar to many cancer patients; hepatomegaly and splenomegaly are detected in one-half of the presenting patients; although the WBC count in AML may be higher or lower than normal, CLL patients always have an elevated WBC count

Non-Hodgkin lymphoma: an extremely variable presentation, but most patients diagnosed in the ED present with a complaint of painless lymphadenopathy; average age of presentation in the United States is 65 years; fever, night sweats, and weight loss are common; patients with more advanced disease at presentation complain of chest, back, or abdominal pain and may have symptoms of spinal cord compression, superior vena cava syndrome, or renal insufficiency; WBC count, RBC count, and platelet count can all be low

Hodgkin lymphoma: classically presented with weight loss, night sweats, and fevers; another classic sign is alcohol intolerance manifested by pruritus, and painful lymphadenopathy shortly after alcohol ingestion; although only 10% of patients have subdiaphragmatic manifestations, most have painless nodes typically described as “rubbery” in the neck and supraclavicular regions

Complications in cancer patients: cancer patients who present to the ED must be evaluated for complications from immunosuppression

Abdominal pain: evaluate for opportunistic infection, intestinal obstruction and/or perforation, and veno-occlusive disease processes (eg, Budd–Chiari syndrome); typhlitis is an enterocolitis that is seen in cases of acute leukemia associated with neutropenia; causes necrosis of the mucosa of the ascending colon and cecum and has a mortality rate of over 50%; CT will show bowel wall thickening and distention of the cecum; broad-spectrum antibiotics, bowel rest, and admission to the surgical service is indicated in the treatment of typhlitis

Respiratory complications: patients with lymphoma and leukemia have higher rates of respiratory complications than with other cancer patients; pneumonia attributable to Streptococcus and H influenzae is the most common cause; lymphoma patients are more usually infected with Pneumocystis jirovecii, mycobacterium, fungus, cytomegalovirus, and herpes simplex virus; although fever is common, cough and sputum production are not; leukemia patients are more likely to develop diffuse alveolar hemorrhage; they present with dyspnea and cough and often with fever, but hemoptysis is rare; chest x-ray shows diffuse interstitial and alveolar infiltrates; diagnosis is made on bronchoscopy

Airway obstruction: far more common secondary to tumor extension or metastatic disease to the trachea, bronchi, or mediastinum; especially true with lymphoma; presenting symptoms include stridor, dyspnea, cough, and hemoptysis; 10% of lymphoma patients also develop a DVT, portending a worse prognosis; patients with hematologic malignant diseases are admitted or discharged depending upon the same complex assessment of risk, benefit, severity of illness, available treatment options, and social situation that are part of the emergency physician’s assessment of every patient; oncologists and hematologists are valuable partners in assessing the disposition of patients; close attention must be paid to adequate and appropriate pain management for all cancer patients; comfort care and end-of-life decisions must be discussed with the patient and the family in conjunction with the inpatient team

Readings

Disclosures

Dr. Moreno-Walton receives grant-research support from Gilead Sciences

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

EMBR170117

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.