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Anemia, Immune-Mediated Hemolytic   61


           •  Anecdotal reports in dogs suggest previous   ○   Splenomegaly from active phagocytosis   Initial Database
                                                  and extramedullary hematopoiesis
             drug administration (e.g., beta-lactam and   •  Intravascular hemolysis  •  CBC  with  microscopic  blood  smear
  VetBooks.ir  IMHA.                            ○   Binding of IgM and IgG immunoglobulins   ○   Decreased hematocrit (HCT), packed cell   Diseases and   Disorders
                                                                                    evaluation
             sulfa antibiotics) may cause a secondary
                                                                                      volume (PCV), RBC count, hemoglobin
                                                  to  the  RBC  membrane  activates  the  c′
           GEOGRAPHY AND SEASONALITY
                                                  membrane with influx of extracellular fluid
           In dogs, increased incidence in the spring (40%   cascade, causing direct damage to the cell   ○   Mild to marked thrombocytopenia
                                                                                    ○   Approximately 50% of dogs with IMHA
           of cases in May and June)              and cell rupture.                   have a nonregenerative or poorly regenera-
                                               •  Potential  causes  of  secondary  IMHA  in    tive anemia at diagnosis.
           ASSOCIATED DISORDERS                 dogs                                ○   Hallmarks of IMHA: spherocytosis (79%
           •  Thromboembolism and pulmonary throm-  ○   Infectious (ehrlichiosis, babesiosis, ana-  of dogs), autoagglutination (42%-66%),
             boembolism (PTE) (very common)       plasmosis, leptospirosis, dirofilariasis)  polychromasia (90%), or some combina-
           •  Disseminated  intravascular  coagulopathy   ○   Neoplasia (lymphoma, histiocytic sarcoma)  tion of these clinical findings in 96% of
             (DIC)                              ○   Drugs (trimethoprim-sulfonamide, penicil-  IMHA dogs.
           •  Thrombocytopenia (<50,000/microL) occurs   lin, cephalosporin).       ○   Moderate to marked leukocytosis with a
             in one-third to one-half of cases (Evans   •  Autoagglutination (antibody-mediated RBC   neutrophilic left shift and/or nucleated
             syndrome).                         clumping),  hallmark  of  IMHA,  primarily   RBCs.
                                                occurs with IgM coating of RBCs.    ○   RBC  parasites:  Babesia spp (dog),  M.
           Clinical Presentation               •  Moderate  to  marked  leukocytosis  with  a   haemofelis (cat), others
           DISEASE FORMS/SUBTYPES               neutrophilic left shift is common in dogs.   •  Serum biochemistry
           •  Primary (idiopathic) IMHA: Immunoglobu-  This neutrophilia is likely due to an increased   ○   Elevated  total  bilirubin,  liver  enzymes
             lins attach to antigens or components of the   release of cells from the bone marrow during   (ALT, alkaline phosphatase [ALP]),
             RBC  membrane,  causing  extravascular   a strong erythroid response and/or cytokine   sometimes blood urea nitrogen (BUN)
             hemolysis, intravascular hemolysis, intravas-  response  to  systemic  inflammation  and/or     ○   Artifactual hypophosphatemia (interfer-
             cular RBC agglutination, and/or activation   necrosis.                   ence from hyperbilirubinemia)
             of the c′ cascade.                •  Hyperbilirubinemia  is  associated  with   ○   Normal total protein with anemia is
           •  Secondary  IMHA:  RBCs  are  destroyed  as   hemolysis (most common) and decreased   consistent with hemolysis.
             innocent bystanders in an immune reaction   hepatic clearance of bilirubin.  •  Urinalysis
             against antigens or foreign proteins attached   •  Elevated  serum  liver  enzymes  (especially   ○   Bilirubinuria and/or hemoglobinuria
             to the cell membrane.              alanine transaminase [ALT]) suggest hypoxic   ○   If pyuria or bacteriuria is present, perform
           •  Extravascular hemolysis: Immunoglobulin   hepatocellular injury.        bacterial culture and sensitivity.
             or c′-coated RBCs are selectively destroyed   •  Moderate  to  marked  thrombocytopenia    •  In cats, FeLV and FIV serologic tests
             by macrophages in the spleen and     could be due to Evans syndrome or early   •  Saline agglutination test (slide autoagglutina-
             liver.                             DIC.                                tion)
           •  Intravascular hemolysis: c′-mediated  RBC   •  Dogs with IMHA are hypercoagulable and   ○   Mix 1 drop of anticoagulated whole blood
             membrane damage causes cell rupture.  at risk for thromboembolism. Increased   with 1 drop of saline on a microscope
                                                liver values, decreased platelet count, and   slide.
           HISTORY, CHIEF COMPLAINT             decreased antithrombin activity are associ-  ○   If enough antibodies are present on the
           •  Signs  of  anemia:  tachycardia,  tachypnea,   ated with thromboembolism in dogs with    cell membrane, RBC  agglutination  can
             dyspnea, lethargy, progressive weakness, collapse  IMHA.                 be identified grossly and microscopically.
           •  Inappetence, anorexia            •  Reticulocytosis is more common in dogs at   •  Coomb’s test (p. 1328), also known as direct
           •  Vomiting, diarrhea                the time of diagnosis than in cats.  antiglobulin/antigen test (DAT): perform if
           •  Discolored   urine   (bilirubinuria   or   ○   Absence of reticulocytes: inadequate time   no visible autoagglutination
             hemoglobinuria)                      for bone marrow response (3-5 days), and/  ○   Direct Coombs’ test detects antibodies
           •  Icterus                             or immune-mediated destruction of RBC   attached to RBCs.
           •  Respiratory distress with acute PTE (p. 842)  precursors              ○   The sensitivity in IMHA is 60%-89%. A
                                                                                      negative Coombs’ test result does not
           PHYSICAL EXAM FINDINGS                                                     exclude a diagnosis of IMHA.
           •  Pale mucous membranes             DIAGNOSIS                         •  Coagulation assessment
           •  Tachycardia                                                           ○   DIC (p. 269)
           •  Tachypnea                        Diagnostic Overview                  ○   Hypercoagulability:  increased  d-dimers
           •  Bounding pulses                  The diagnosis is supported by findings of   and/or fibrin degradation products (FDPs),
           •  Icterus                          anemia, hemolysis (hemoglobinemia or hemo-  decreased fibrinogen, decreased antithrombin
           •  Heart murmur (systolic, left base)  globinuria), evidence of antibodies directed   •  Abdominal radiographs
           •  Hepatomegaly and/or splenomegaly  against RBC (autoagglutination, spherocytosis,   ○   Evaluate spleen and liver size.
           •  If Evans syndrome or DIC, possible petechiae   or positive Coombs’ test), and response to   ○   Identify an underlying cause for secondary
             and/or ecchymosis                 immunosuppressive  therapy.  No  finding  is   IMHA.
                                               pathognomonic for primary IMHA, and causes   ○   Identify metallic (zinc) gastrointestinal
           Etiology and Pathophysiology        of secondary IMHA must be investigated as   foreign bodies as a cause of non–immune-
           •  Extravascular hemolysis          relevant (e.g., retroviral testing of cats, vector-  mediated hemolysis.
             ○   Commonly occurs in the spleen (occasion-  borne disease testing based on geography).  •  Abdominal ultrasonography
               ally liver).                                                         ○   Identify an underlying cause (neoplasia)
             ○   Immunoglobulin (Ig), mainly IgG,   Differential Diagnosis            of secondary IMHA.
               attach to RBC and cause phagocytosis;   Anemia:                    •  Thoracic radiographs
               minimal c′-mediated cell membrane     •  Other hemolytic anemias (p. 59)  ○   Usually unremarkable; marked pulmonary
               damage                          •  Hemorrhage (p. 433)                 interstitial pattern, patchy alveolar opaci-
             ○   Partial erythrophagocytosis can cause   •  Bone marrow disorder, chronic disease  ties, and mild pleural effusion might be
               spherocytes, a hallmark of IMHA.  Icterus (p. 528)                     associated with a PTE.

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