Page 831 - Williams Hematology ( PDFDrive )

806 Part VI: The Erythrocyte Chapter 51: Fragmentation Hemolytic Anemia 807

DIFFERENTIAL DIAGNOSIS physical exertion in the upright position, occasionally accompanied by
Factors that can promote valve-associated hemolysis or worsen the nausea, abdominal cramps, aching in the back or legs, a “stitch in the
resultant anemia include iron deficiency (Chap. 43), because anemia side,” or a burning feeling in the soles of the feet. Physical examination is
increases cardiac output and shear stress and iron-poor red cells are usually unrevealing, although hepatosplenomegaly and transient jaun-
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more fragile than normal; folate deficiency (Chap. 41) arising from dice have been rarely reported.
increased erythropoiesis; anemia of chronic disease because of endo- Davidson proved definitively in 1969 that march hemoglobinuria
carditis; anticoagulant-induced gastrointestinal hemorrhage (Chaps. 37, is caused by red cell trauma within the vessels of the soles of the feet,
133, and 134); and increased cardiac output as a consequence of stren- and its severity is influenced by the hardness of the running surface,
uous physical exertion. 82 the distance run, the heaviness of the athlete’s stride, and the protective
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adequacy of his footwear. In addition, he showed that the condition
could be prevented by using padded insoles, a finding later substanti-
THERAPY ated by other authors. 106,107 Hemoglobinuria has also been seen follow-
Appropriate therapy for hemolytic anemia arising from valvular dys- ing other types of trauma in activities as diverse as repetitive slapping of
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108
function consists of iron and folate replacement (if deficient) and surgical the forehead, karate exercises, basketball followed by congo drum
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repair or replacement of the malfunctioning prosthesis (if indicated). playing, and kendo (a Japanese martial art where heavily padded
Poor surgical candidates with perivalvular leaks may benefit from per- combatants strike each other repeatedly with bamboo swords). 103
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cutaneous closure with an Amplatzer occluder device. Adjunctive Because the estimated quantity of blood hemolyzed in an average
measures to be tried include β-blockade to slow the velocity of the circu- paroxysm is only 6 to 40 mL, anemia is uncommon and if present is
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lation, erythropoietin therapy to stimulate erythropoiesis further, and usually mild ; however repeated episodes can cause iron deficiency,
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pentoxifylline therapy to increase the deformability of red cells. 91 which may lead to or accentuate anemia (Chap. 43). Morphologic evi-
Although some authors have not found the use of pentoxifylline dence of red cell damage is not seen, although one patient was found
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to be beneficial, several case reports have described amelioration of to have poikilocytes and occasional “four-leaf clover” cells after exer-
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valve-related hemolysis and resultant decreased need for red cell trans- cise. Renal damage is also not commonly seen, but cases of acute
fusion in patients receiving pentoxifylline. 93–95 A prospective study tubular necrosis and resultant acute renal insufficiency have been
of 40 individuals with double (mitral and aortic) valve replacements described. 112–115
randomized patients to receive either no treatment or pentoxifylline
400 mg orally three times daily for 120 days. The group who received pen- KASABACH-MERRITT PHENOMENON
toxifylline had significantly higher hemoglobin and haptoglobin levels,
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and significantly lower LDH, total and indirect bilirubin, and corrected First described in 1940, the Kasabach-Merritt phenomenon is a syn-
reticulocyte levels, after 4 months of treatment. Of the nine patients with drome that usually develops in early childhood, and is characterized
severe hemolysis (LDH >1500 U/L), six individuals had amelioration by thrombocytopenia, MAHA, consumptive coagulopathy, and hypo-
or complete resolution of their disease, while three patients’ hemolysis fibrinogenemia caused by an enlarging kaposiform hemangioendo-
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persisted unchecked, suggesting that pentoxifylline therapy is beneficial thelioma or tufted angioma. Kaposiform hemangioendotheliomas
in more than 60 percent of those with valve-related hemolysis. 96 are highly aggressive, vascular tumors that occur equally in males and
Between 15 and 30 percent of patients will develop black pig- females, and show little tendency to resolve spontaneously. They can be
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ment gallstones following valve surgery, the majority occurring within locally invasive but have never been reported to metastasize. Com-
6 months of the procedure. Whether this is a result of acute hemolysis plications can include hemothorax or pericardial effusion. 118,119 It is
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associated with use of the heart–lung machine or chronic hemolysis postulated that endothelial cell abnormalities and vascular stasis lead
because of the valve replacement itself 98,99 is uncertain; however, therapy to activation of platelets and the coagulation cascade within the tumor’s
with ursodeoxycholic acid 600 mg daily beginning 1 week before sur- vessels, with subsequent depletion of both platelets and clotting factors.
gery significantly decreases the incidence of gallstone formation from Microangiopathic hemolytic anemia results from mechanical trauma
approximately 29 percent in those who were left untreated to approxi- sustained by the erythrocytes traversing the tumor’s abnormal, partially
mately 8 percent (P <0.01). 100 thrombosed vascular channels. 120
Although numerous therapies are used, the mortality rate of
Kasabach-Merritt phenomenon can be as high as 30 percent. Even
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COURSE AND PROGNOSIS though surgical resection is always followed by normalization of hema-
Evidence of hemolysis can be seen within days or weeks 64,76,80 following tologic parameters, many lesions are too large to be resected with-
60
valve surgery. If reoperation is required, reported mortality rates range out severe disfigurement. Other treatments include glucocorticoids,
between 0 and 6 percent, 75,101 and hemolytic anemia can occasionally interferon-α, antifibrinolytic agents, and the antiplatelet agents ticlo-
recur. 60,101 pidine and aspirin, low-molecular-weight heparin, embolization,
radiation, laser therapy, and chemotherapy using vincristine, cyclo-
OTHER CAUSES OF NONIMMUNE phosphamide, actinomycin D, or methotrexate. 117,118,120,122,123
HEMOLYSIS
MISCELLANEOUS
MARCH HEMOGLOBINURIA Microangiopathic hemolytic anemia has also been seen in malig-
In 1881, Fleischer described a German soldier in whom hemoglobi- nant systemic hypertension, pulmonary hypertension, giant cavern-
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nuria was brought on by marching. Although usually reported in ous hemangiomas of the liver, and various vasculitides, including
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young males, no doubt explained by their more frequent participation Wegener granulomatosis 125,126 and giant cell arteritis. Osmotically
in severe and prolonged exertion, it can also be seen in women. 103,104 The induced hemolysis has occurred when distilled water is used as an irri-
presenting complaint is passage of dark urine immediately following gant during transurethral resection of the prostate. 128

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