Cold antibody immunohemolytic anemia usually is caused by low-affinity IgM antibodies that bind to red cell membranes only at temperatures below 30°C, such as occur in distal parts of the body (e.g., ears, hands, and toes) in cold weather. Although bound IgM fixes complement, the latter steps of the complement cascade occur inefficiently at temperatures lower than 37°C. As a result, most cells with bound IgM pick up some C3b but are not lysed intravascularly. When these cells travel to warmer areas, the weakly bound IgM antibody is released, but the coating of C3b remains. Because C3b is an opsonin (Chapter 2), the cells are phagocytosed by macrophages, mainly in the spleen and liver; hence, in most cases the hemolysis is mainly extravascular. Binding of pentavalent IgM also crosslinks red cells and causes them to clump (agglutinate). Sludging of blood in capillaries because of agglutination often produces Raynaud phenomenon in the extremities of affected individuals. Cold agglutinins sometimes also appear transiently during recovery from pneumonia caused by Mycoplasma spp. and infectious mononucleosis, producing a mild anemia of little clinical importance. More important, chronic forms of cold agglutinin hemolytic anemia occur in association with certain B cell neoplasms or as an idiopathic condition.
Hemolysis of red cells due to their exposure to abnormal mechanical forces occurs in two major settings. Clinically significant traumatic hemolysis is sometimes produced by defective cardiac valve prostheses, which may create sufficiently turbulent blood flow to shear red cells (the blender effect). More commonly, it occurs incidentally during an activity involving repeated physical pounding of one or more body parts (e.g., marathon racing, karate chopping, bongo drumming). Microangiopathic hemolytic anemia is observed in pathologic states in which small vessels become partially obstructed or narrowed by lesions that predispose passing red cells to mechanical damage. The most frequent of these conditions is disseminated intra-vascular coagulation (DIC) (see later), in which vessels are narrowed by the intravascular deposition of fibrin. Other causes of microangiopathic hemolytic anemia include malignant hypertension, systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and disseminated cancer. Mechanical fragmentation of red cells (schistocytosis) leads to the appearance of characteristic “burr cells,” “helmet cells,” and “triangle cells” in peripheral blood smears (
Fig.
12.7 ). Although microangiopathic hemolysis is not usually a major clinical problem in and of itself, it often points to a serious underlying condition.
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Fig. 12.7 Microangiopathichemolyticanemia—peripheralbloodsmear.Thisspecimenfromapatientwithhemolyticuremicsyndromecontainsseveralfragmentedredcells.(Courtesy of Dr.Robert W. McKenna,Department of Pathol-ogy,University of Texas Southwestern Medical School,Dallas,Texas.)
It is estimated that malaria affects 500 million and kills more than 1 million people per year, making it one of the most serious afflictions of humans. Malaria is endemic in Asia and Africa, but with widespread jet travel cases are now seen all over the world. It is caused by one of five types of protozoa. Of these, the most important is Plasmodium falciparum, which causes tertian malaria (falciparum malaria), a disorder with a high fatality rate. The other four species of Plasmodium that infect humans—Plasmodium malariae, Plasmodium vivax, Plasmodium knowlesi, and Plasmodium ovale—cause relatively benign disease. All forms are transmitted by the bite of female Anopheles mosquitoes, and humans are the only natural reservoir.