Andrew Mackin 安德魯·麥金
BVMS, DVSc, DACVIM 獸醫學士、獸醫科學博士、美國獸醫內科學院認證醫師
Dr. Mackin is professor and head of the Department of Clinical Sciences at Mississippi State University College of Veterinary Medicine. He received his BVMS degree at Murdoch University in Australia, completed an internship and residency at the University of Melbourne, and an internal medicine residency at Ontario Veterinary College. His research focuses on hematology, immunosuppressive therapy, and transfusion medicine.
Read Articles Written by Andrew Mackin
Immune-mediated hemolytic anemia (IMHA) is one of the more commonly encountered causes of anemia in dogs and cats. IMHA can affect animals of any age, but it most commonly affects young adult and middle-aged dogs and cats.
免疫介導性溶血性貧血(IMHA)是犬貓貧血較常見的病因之一。IMHA 可發生於任何年齡的動物,但最常見於年輕成年及中年犬貓。
The condition can either be primary (nonassociative), in which the immune disease has no known causative trigger, or secondary (associative), in which the trigger or cause is an underlying condition.1 Practically speaking, although a cause for secondary IMHA can often be suspected on the basis of a temporal association with drug administration or underlying disease, proving causation is usually impossible. Although primary and secondary IMHA occurs in dogs and cats, primary IMHA is more common in dogs and secondary IMHA is more common in cats.
此病症可分為原發性(非關聯性),即免疫疾病無已知誘發因素;或繼發性(關聯性),其誘因來自潛在疾病。 1 實際上,雖然繼發性 IMHA 的病因常可透過與藥物使用或潛在疾病的時間關聯性來推測,但通常無法確證因果關係。雖然原發性和繼發性 IMHA 在犬貓皆會發生,但原發性 IMHA 較常見於犬隻,而繼發性 IMHA 較常見於貓隻。
Primary IMHA: Although it has no obvious identifiable cause, primary IMHA is associated with an inherited predisposition in dogs, most commonly cocker spaniels, springer spaniels, and poodles.
原發性 IMHA:雖然無明顯可識別病因,但原發性 IMHA 與犬隻的遺傳傾向有關,最常見於可卡犬、史賓格犬和貴賓犬。
Secondary IMHA: Associative IMHA has been strongly linked with organisms that infect red blood cells (RBCs) (e.g., Babesia species in dogs and Mycoplasma haemofelis in cats) and much more speculatively with feline leukemia virus infection, medications (particularly sulfur drugs in dogs and antithyroid medications in cats), recent vaccination, or neoplasia.1 Suspected secondary IMHA may also follow bee stings and elapid snake bites.2,3 However, for many of these proposed potential triggers, causation has not been definitively established.
續發性免疫介導溶血性貧血(IMHA):關聯性 IMHA 已明確與感染紅血球(RBCs)的病原體相關(例如犬隻的巴貝斯蟲屬及貓的貓血黴漿菌),而與貓白血病病毒感染、藥物(特別是犬隻的磺胺類藥物及貓的抗甲狀腺藥物)、近期疫苗接種或腫瘤的關聯性則更具推測性。 1 疑似續發性 IMHA 也可能發生於蜜蜂叮咬及眼鏡蛇科蛇咬後。 2,3 然而,對於許多這些被提出的潛在觸發因子,其因果關係尚未明確確立。
Pathophysiology oF IMHA IMHA 的病理生理學
IMHA in dogs and cats is an antibody-mediated disease. It’s a classic example of a cytotoxic (type II) immune-mediated reaction in which antibody and complement attachment to the surface of RBCs leads to hemolysis. Hemolysis can be extravascular (antibody-coated RBCs are recognized and phagocytosed by macrophages in organs such as the spleen) or intravascular (antibody and complement on the RBC surface lead to direct cell lysis within the circulation).
犬貓的 IMHA 是一種抗體介導疾病。它是細胞毒性(第二型)免疫介導反應的典型例子,其中抗體和補體附著於紅血球表面導致溶血。溶血可以是血管外的(被抗體包覆的紅血球被脾臟等器官中的巨噬細胞識別並吞噬)或血管內的(紅血球表面的抗體和補體導致循環系統內的直接細胞溶解)。
Extravascular hemolysis: With the more common extravascular hemolysis, hemoglobin is released inside macrophages and eventually metabolized to bilirubin. Excessive bilirubin production can sometimes overwhelm hepatobiliary metabolic pathways, leading to hyperbilirubinemia and jaundice (FIGURE 1). Many patients with IMHA, however, never become clinically jaundiced.
血管外溶血:較常見的血管外溶血中,血紅素會在巨噬細胞內釋放並最終代謝為膽紅素。過量的膽紅素產出有時會超過肝膽代謝途徑的負荷,導致高膽紅素血症和黃疸(圖 1)。然而,許多患有免疫介導溶血性貧血(IMHA)的病患從未出現臨床黃疸症狀。

Figure 1. Severe jaundice in a schnauzer that had received multiple transfusions for IMHA.
圖 1. 一隻因 IMHA 接受多次輸血的雪納瑞犬出現嚴重黃疸。
Intravascular hemolysis: With the less common intravascular hemolysis, intracellular hemoglobin is released directly into the circulation, leading to hemoglobinemia, hemoglobinuria, and potentially kidney damage caused by hemoglobinuric nephrosis.
血管內溶血:較少見的血管內溶血中,細胞內血紅素會直接釋放到循環系統,導致血紅素血症、血紅素尿,並可能因血紅素尿性腎病變造成腎臟損傷。
Intuitively, because hemolysis involves peripheral destruction of RBCs, resultant anemia would be expected to be highly regenerative as the marrow responds (within 3 to 5 days) by maximizing production of new RBCs.
直觀而言,由於溶血涉及紅血球(RBCs)的外周破壞,隨之產生的貧血預期會呈現高度再生性反應,因為骨髓會在 3 至 5 天內通過最大化新生紅血球的產量來應對。
However, some cases of IMHA are actually poorly regenerative, either because antibodies against RBCs are also directed against marrow erythroid precursors or because the inflammation associated with IMHA leads to a functional iron deficiency (anemia of chronic disease).4
然而,某些免疫介導性溶血性貧血(IMHA)病例實際上再生能力不佳,這可能是因為抗紅血球抗體同時攻擊骨髓中的紅系前驅細胞,或是因為 IMHA 相關的炎症導致功能性鐵缺乏(慢性疾病性貧血)。 4
Clinical Presentation of IMHA
免疫介導性溶血性貧血的臨床表現
Most commonly, dogs and cats with IMHA exhibit clinical features suggestive of moderate to severe anemia: pale mucous membranes, lethargy, exercise intolerance, and collapse. Physical examination will often reveal tachycardia, tachypnea, and strong (bounding) pulses associated with the sympathetic stimulation triggered by local tissue hypoxia.
最常見的情況是,患有 IMHA 的犬貓會表現出中度至重度貧血的臨床特徵:黏膜蒼白、嗜睡、運動不耐受和虛脫。理學檢查通常會發現因局部組織缺氧引發的交感神經刺激所導致的心搏過速、呼吸急促和強勁(跳躍式)脈搏。
Patients with severe anemia often have a grade 1 to grade 2 systolic left-sided (hemic) murmur. Some patients with extravascular hemolysis will exhibit mild to marked jaundice, and patients with intravascular hemolysis will have hemoglobinemia (red-pink serum) and hemoglobinuria (dark “port wine” urine) (FIGURE 2).
嚴重貧血患者常出現 1 至 2 級收縮期左側(血液性)心雜音。部分血管外溶血患者會呈現輕度至明顯黃疸,而血管內溶血患者則會出現血紅素血症(血清呈紅粉色)和血紅素尿(尿液呈深「波特酒」色)(圖 2)。

Figure 2. Necropsy images from a dog with severe intravascular hemolysis, demonstrating typical “port wine” appearance of hemoglobinuria (syringe) and dark discoloration of kidneys (“gun metal” kidneys) associated with hemoglobinuric nephrosis.
圖 2. 一隻患有嚴重血管內溶血犬隻的屍檢影像,顯示典型的「波特酒色」血紅蛋白尿(注射器內)以及與血紅蛋白尿性腎病相關的腎臟深色變色(「槍金屬色」腎臟)。
Some patients also show signs consistent with enhanced inflammatory and mononuclear phagocytic processes, including inappetence, a low-grade fever, mild lymphadenopathy, and palpable splenomegaly. Such signs are often erroneously interpreted as evidence of infection.
部分病患還會出現與炎症反應增強及單核吞噬細胞系統活化相符的徵狀,包括食慾不振、低度發燒、輕微淋巴結腫大以及可觸及的脾腫大。這些徵狀常被錯誤解讀為感染的證據。
Occasionally, affected animals will have Evans syndrome, a combination of IMHA and immune-mediated thrombocytopenia; these patients may exhibit bleeding in the form of cutaneous and mucosal petechiae and ecchymoses, melena, and hematuria. A common complication of IMHA is pulmonary thromboembolism; affected patients will often exhibit acute onset of dyspnea.
偶爾,患病動物會出現伊凡氏症候群,即免疫介導性溶血性貧血合併免疫介導性血小板減少症;這類病患可能表現出皮膚及黏膜瘀點、瘀斑、黑便及血尿等出血症狀。免疫介導性溶血性貧血的常見併發症是肺血栓栓塞;受影響病患通常會突然出現呼吸困難。
Diagnosis of IMHA 免疫介導性溶血性貧血的診斷
Minimum Database 基本檢測項目
Many diagnostically helpful clues can be provided by a complete blood count (CBC), serum biochemistry, and urinalysis.
完整的全血細胞計數(CBC)、血清生化檢查和尿液分析可提供許多有助於診斷的線索。
Complete Blood Count 全血細胞計數
A CBC may reveal anemia, an inflammatory leukogram, and/or thrombocytopenia.
全血細胞計數可能顯示貧血、炎症性白血球像和/或血小板減少症。
Anemia: Anemia may be mild to marked, usually with features of a regenerative response such as anisocytosis and polychromasia and associated RBC indices such as increased mean corpuscular volume and decreased mean corpuscular hemoglobin concentration.
貧血:貧血程度可能從輕微到顯著不等,通常會伴隨再生性反應的特徵,如紅血球大小不均和多染性,以及相關的紅血球指數變化,例如平均紅血球體積增加和平均紅血球血紅素濃度降低。
- Marked autoagglutination, which is common in IMHA patients, can lead to inaccuracies in hematocrit, RBC counts, and other RBC indices.
明顯的自體凝集現象在 IMHA 患者中相當常見,可能導致血容比、紅血球計數和其他紅血球指數的測量不準確。 - Reticulocytes most commonly increase; however, in up to one-third of IMHA patients, reticulocytes decrease.
網狀紅血球通常會增加;然而,在近三分之一的 IMHA 患者中,網狀紅血球反而會減少。 - Analysis by automated hematology analyzers should be accompanied by direct examination of a stained blood smear for diagnostically useful features (e.g., spherocytes and ghost cells) and for conditions that trigger or mimic IMHA (e.g., babesiosis, mycoplasmosis, Heinz body hemolytic anemia, and microangiopathic hemolytic anemia [schistocytes]).
使用自動血液分析儀進行分析時,應同時配合染色血液抹片的直接鏡檢,以觀察具有診斷價值的特徵(例如球形紅血球和鬼影細胞),以及可能引發或類似 IMHA 的狀況(例如巴貝斯蟲病、黴漿菌感染、海因茲小體溶血性貧血和微血管病性溶血性貧血[碎裂紅血球])。
The presence of spherocytes is strongly suggestive of IMHA. Spherocytes are small spherical RBCs that have lost their usual disk shape and central pallor. Spherocytes in IMHA patients are formed when phagocytes remove a piece of RBC membrane during attempted phagocytosis.
出現球形紅血球強烈暗示免疫介導性溶血性貧血(IMHA)。球形紅血球是失去正常雙凹圓盤形狀及中央蒼白區的小型球狀紅血球,在 IMHA 患者中,當吞噬細胞試圖吞噬時移除部分紅血球膜而形成。
Spherocytes are readily recognizable among the normal larger disk-shaped RBCs of dogs but are not easily identified in cats. The presence of ghost cells in freshly processed samples strongly suggests intravascular hemolysis. Ghost cells are hollow membrane remnants of RBCs that have been emptied of hemoglobin.
球形紅血球在犬隻正常較大的圓盤狀紅血球中容易辨識,但在貓科動物中不易辨認。新鮮處理樣本中出現影細胞強烈暗示血管內溶血。影細胞是紅血球被排空血紅素後留下的中空膜殘骸。
However, in blood for which sample preparation was delayed, ghost cells are a common and diagnostically meaningless artifact.
然而,在延遲製備的血液樣本中,影細胞是常見且無診斷意義的人工產物。
Inflammatory Leukogram: A CBC will often also reveal a mild to marked inflammatory leukogram associated with the inflammation caused by immune-mediated RBC destruction. An inflammatory leukogram in patients with suspected IMHA, however marked, should not be misinterpreted as evidence of infection.
炎症性白血球像:全血細胞計數(CBC)通常也會顯示因免疫介導紅血球破壞引起的輕度至顯著炎症性白血球像。但對於疑似 IMHA 患者,無論炎症性白血球像多麼顯著,都不應誤解為感染證據。
Neutrophilia is sometimes profound and can mimic the extreme neutrophil counts seen with granulocytic leukemia (so-called leukemoid response).
嗜中性球增多症有時會非常顯著,可能類似於顆粒球性白血病所見的極高嗜中性球計數(所謂的類白血病反應)。
Thrombocytopenia: Platelet counts in IMHA patients are occasionally low.
血小板減少症:IMHA 患者的血小板計數偶爾會偏低。
Mild to moderate thrombocytopenia (<150,000 platelets/µL) is common, affecting about 55% of IMHA patients, and is most likely associated with platelet consumption within thrombi.5
輕度至中度血小板減少症(<150,000 血小板/µL)相當常見,影響約 55%的 IMHA 患者,最可能與血栓內的血小板消耗有關。 5
Marked thrombocytopenia (<50,000 platelets/µL) is less common, affecting about 25% of IMHA patients, and may indicate Evans syndrome.5-7
顯著血小板減少症(<50,000 血小板/µL)較不常見,影響約 25%的 IMHA 患者,可能表示患有 Evans 症候群。 5-7
Serum Biochemistry 血清生化檢查
Serum biochemistry will often reveal mild to marked hyperbilirubinemia in about 66% of IMHA patients and elevated liver enzymes in more than 50% of patients.8
血清生化檢查通常會顯示約 66%的免疫介導性溶血性貧血(IMHA)患者有輕度至顯著的高膽紅素血症,超過 50%的患者肝臟酵素會升高。 8
- Bilirubinemia is not present in all IMHA patients; it is most common in those that have severe acute hemolysis or have had multiple transfusions.
並非所有 IMHA 患者都會出現膽紅素血症,這種情況最常見於嚴重急性溶血或接受過多次輸血的患者。 - Liver enzymes, particularly alanine aminotransferase (ALT), will often be mildly to moderately elevated, possibly caused by hepatic hypoxia.
肝臟酵素,特別是丙氨酸轉氨酶(ALT),通常會輕度至中度升高,這可能是由肝臟缺氧所引起。 - Hemoglobinemia may be noted by visual inspection of the serum of patients with intravascular hemolysis and can interfere with other serum biochemistry results.
血管內溶血患者的血清可通過目視檢查發現血紅蛋白血症,此現象可能干擾其他血清生化檢驗結果。 - Serum protein levels in IMHA patients are typically within normal limits and, if low, may suggest undetected bleeding rather than hemolysis as the cause of anemia.
免疫介導性溶血性貧血(IMHA)患者的血清蛋白水平通常處於正常範圍內,若偏低則可能暗示未被發現的出血(而非溶血)才是貧血的原因。 - Marked hypophosphatemia may be identified as a nonimmune cause of hemolytic anemia, particularly in patients receiving treatment for diabetic ketoacidosis or in those with suspected refeeding syndrome.
顯著低磷血症可能被確認為溶血性貧血的非免疫性病因,特別見於接受糖尿病酮酸中毒治療的患者或疑似再餵食症候群的個案。
Urinalysis 尿液分析
Urinalysis results for IMHA patients are typically within normal limits, apart from dipstick detection of bilirubinuria or hemoglobinuria in some patients. Dipstick evaluation may lead to misinterpretation of hemoglobinuria as hematuria, but urine sediment examination will confirm the absence of RBCs, thereby ruling out hematuria.
免疫介導性溶血性貧血(IMHA)患者的尿液分析結果通常正常,部分患者可能出現試紙檢測出膽紅素尿或血紅蛋白尿的情況。試紙評估可能導致將血紅蛋白尿誤判為血尿,但尿液沉渣鏡檢可確認紅血球(RBCs)不存在,從而排除血尿的可能性。
Diagnostic Imaging 診斷影像學
Diagnostic imaging (chest and abdominal radiography and abdominal ultrasonography) is not an essential diagnostic tool for patients with suspected IMHA and often reveals no significant abnormalities.
對於疑似免疫介導性溶血性貧血(IMHA)的病患,診斷影像學(胸腔與腹部放射線攝影及腹部超音波檢查)並非必要的診斷工具,且通常不會顯示明顯異常。
The main purpose of diagnostic imaging is to rule out conditions that mimic or trigger IMHA (e.g., zinc toxicity) or underlying neoplasia causing either associative IMHA (most commonly suspected with round cell tumors) or nonimmune microangiopathic hemolytic anemia (often seen with hemangiosarcoma).
診斷影像學的主要目的在於排除可能模仿或誘發 IMHA 的病症(例如鋅中毒),或是可能導致關聯性 IMHA(最常見於圓形細胞腫瘤)或非免疫性微血管病性溶血性貧血(常見於血管肉瘤)的潛在腫瘤病變。
Abdominal images of patients with primary IMHA are often unremarkable but may sometimes reveal splenomegaly, most likely caused by increased activity of the mononuclear phagocytic system. Ultrasonography may reveal thrombus formation in the vasculature of organs such as the spleen. Mild abdominal effusion is sometimes noted.
原發性 IMHA 病患的腹部影像通常無特殊發現,但有時可能顯示脾腫大,這很可能是單核吞噬細胞系統活性增加所致。超音波檢查可能發現脾臟等器官血管內的血栓形成。偶爾可觀察到輕度腹腔積液。
For any dyspneic IMHA patient with normal or near-normal thoracic radiographs, pulmonary thromboembolism should be strongly suspected.
對於任何出現呼吸困難且胸部 X 光檢查結果正常或接近正常的 IMHA 患者,應高度懷疑肺血栓栓塞症。
Although pulmonary thromboembolism can be radiographically silent, sometimes enlarged pulmonary arteries, focal interstitial or alveolar lung patterns, focal areas of lung hyperlucency caused by reduced blood flow distal to the thrombus (oligemia), and/or mild pleural effusion are observed (FIGURE 3). Suspected pulmonary thromboembolism can be confirmed, if needed, by use of advanced imaging techniques such as contrast-enhanced computed tomography and pulmonary scintigraphy.
雖然肺血栓栓塞症在 X 光下可能無明顯徵象,但有時可觀察到肺動脈擴張、局部間質性或肺泡性肺型態變化、血栓遠端血流減少導致的局部肺區過度透亮(少血徵象),以及/或輕度胸膜積液(圖 3)。如有需要,可透過對比增強電腦斷層掃描和肺閃爍掃描等先進影像技術確診疑似肺血栓栓塞症。
Immunologic Testing 免疫學檢測
Strictly speaking, diagnosis of IMHA requires confirmation of the immune-mediated nature of the disease. Although many different immunologic tests have been used over the years, 2 particular tests have stood the test of time: in-saline agglutination testing and Coombs’ testing.
嚴格來說,免疫介導性溶血性貧血(IMHA)的診斷需要確認疾病的免疫介導性質。雖然多年來使用了許多不同的免疫學檢測,但有兩種特定檢測經得起時間考驗:生理鹽水凝集試驗和庫姆斯試驗。
In-Saline Agglutination Testing: In many patients with IMHA, particularly those with high levels of antibody bound to cell membranes, RBCs can be strongly adhered to each other by antibodies attached to more than one RBC. Resultant RBC autoagglutination is noted by visible red speckles in anticoagulated blood (FIGURE 4) and by rapid separation of RBCs from plasma in blood samples that stand in tubes without mixing.
生理鹽水凝集試驗:在許多 IMHA 患者中,特別是那些細胞膜上結合高濃度抗體的患者,紅血球可能因附著於多個紅血球上的抗體而強烈相互黏附。由此產生的紅血球自體凝集可通過抗凝血中可見的紅色斑點(圖 4)以及未混合試管中血樣紅血球與血漿快速分離來觀察。
This immune-mediated agglutination process is so strong that no amount of washing with saline will separate attached RBCs, whereas rouleaux formation (another process that causes RBCs to adhere to each other in sick patients and leads to visible speckles) is readily dispersed by saline.
這種免疫介導的凝集作用非常強烈,即使使用生理鹽水反覆沖洗也無法分離黏附的紅血球;而縉錢狀排列(另一種會使患病動物紅血球相互黏附並形成可見斑點的現象)則很容易被生理鹽水分散。
A positive in-saline agglutination test, therefore, strongly suggests a diagnosis of IMHA and is often thought to indicate a more severe disease process.
因此,生理鹽水凝集試驗呈陽性結果強烈提示免疫介導性溶血性貧血(IMHA)的診斷,且通常被認為代表更嚴重的疾病進程。

FIGURE 4. Red speckles caused by autoagglutination in a heparinized tube of blood from a dog with severe IMHA.
圖 4. 來自嚴重 IMHA 患犬的肝素抗凝血液試管中,由自體凝集作用造成的紅色斑點。
The simplest in-clinic version of in-saline agglutination testing is the slide agglutination test, in which 4 to 10 drops of saline are added to 1 drop of anticoagulated blood on a microscope slide (FIGURE 5) and the sample is gently mixed by tilting the slide while watching for gross agglutination (speckles) (FIGURE 6). The test should be performed with saline and blood at or above room temperature to avoid an erroneous false-positive result caused by cold agglutination, a result of dubious diagnostic significance. If gross agglutination is not observed, a cover slip is placed over the sample and the slide is inspected microscopically for microagglutination (strongly adhered RBC clumps).
最簡易的院內生理鹽水凝集試驗版本是玻片凝集試驗,其操作方式為在顯微鏡載玻片上(圖 5)將 4 至 10 滴生理鹽水加入 1 滴抗凝血滴中,並通過傾斜玻片輕柔混合樣本,同時觀察肉眼可見的凝集現象(斑點狀)(圖 6)。試驗應在生理鹽水與血液處於室溫或更高溫度下進行,以避免因冷凝集作用導致無診斷意義的假陽性結果。若未觀察到肉眼凝集,則需在樣本上覆蓋蓋玻片,並透過顯微鏡檢查微凝集現象(緊密黏附的紅血球團塊)。
Both gross and microscopic agglutination support a diagnosis of IMHA. In-saline agglutination test specificity can be increased by adding saline washing steps before assessing for agglutination.9 Because RBC agglutination does not occur in many IMHA patients, a negative in-saline agglutination test result does not rule out IMHA.
無論肉眼或顯微鏡下的凝集現象均支持免疫介導性溶血性貧血(IMHA)的診斷。在評估凝集前增加生理鹽水洗滌步驟可提升生理鹽水凝集試驗的特異性。由於許多 IMHA 患者並不會出現紅血球凝集,因此陰性的生理鹽水凝集試驗結果不能排除 IMHA。

FIGURE 5. In-saline slide agglutination test process. A drop of EDTA anticoagulated blood has already been added to a microscope slide, and 4 drops of saline are being added.
圖 5. 生理鹽水玻片凝集試驗流程。已將一滴 EDTA 抗凝血加入顯微鏡玻片,並正在加入 4 滴生理鹽水。

FIGURE 6. Strong positive in-saline slide agglutination in blood from a jaundiced dog with IMHA; red speckles persist despite addition of saline.
圖 6. 患有 IMHA 的黃疸犬隻血液顯示強陽性生理鹽水玻片凝集反應;即使加入生理鹽水後仍持續存在紅色顆粒。
Coombs’ Testing: The most common send-out test used to confirm a diagnosis of IMHA is the Coombs’ test, or direct antiglobulin test (DAT), which detects antibodies and/or complement bound to RBC membranes. Many laboratories use a polyvalent mix of antibodies directed against IgG, IgM, and complement.
庫姆斯試驗(Coombs' test):最常用於確診 IMHA 的外送檢驗是庫姆斯試驗,或稱直接抗球蛋白試驗(DAT),可檢測結合在紅血球膜上的抗體和/或補體。許多實驗室使用針對 IgG、IgM 和補體的多價抗體混合物。
The end point of the DAT is RBC agglutination, and addition of antibodies that bind to IgG, IgM, or complement on the cell membrane increases the number of antibodies bound to RBCs, leading to agglutination in samples that would otherwise not have true autoagglutination.
DAT 的終點是紅血球凝集反應,加入能與細胞膜上 IgG、IgM 或補體結合的抗體,可增加結合在紅血球上的抗體數量,從而使原本不會發生真正自體凝集的樣本產生凝集反應。
Test sensitivity is therefore increased compared with slide agglutination, albeit with potentially decreased test specificity. With use of a polyvalent mix of antibodies, DAT sensitivity is reported to typically range from 60% to a little over 80%, and test specificity is generally 95% or above.10,11 Modifications to the standard DAT that may increase diagnostic value include running the test at different temperatures and a wide range of titers and using individual monovalent antibodies against IgG, IgM, IgA, and complement as well as a standard polyvalent antibody/complement mix.
因此,與玻片凝集試驗相比,此檢測的敏感度有所提高,儘管可能伴隨特異性的降低。使用多價抗體混合物時,直接抗球蛋白試驗(DAT)的敏感度通常報告為 60%至略高於 80%,而檢測特異性一般為 95%或以上。 10,11 可能提升標準 DAT 診斷價值的改良方法包括:在不同溫度下進行測試、使用廣泛的效價範圍、採用針對 IgG、IgM、IgA 和補體的單價抗體,以及標準的多價抗體/補體混合物。
Because, depending on the method used, the diagnostic accuracy of the DAT can vary from mediocre to highly accurate, a patient can potentially have IMHA despite a negative DAT result.10 Diagnostic accuracy of the DAT may be affected by prior corticosteroid therapy or transfusion.
由於所採用的方法不同,DAT 的診斷準確性可能從普通到高度準確不等,因此即使 DAT 結果呈陰性,患者仍可能患有免疫介導性溶血性貧血(IMHA)。 10 DAT 的診斷準確性可能受到先前皮質類固醇治療或輸血的影響。
Because the DAT is typically a send-out test in which results are invariably delayed, treatment for critical patients with suspected IMHA should be based on clinical suspicion and not delayed until results return. Arguably, if an in-saline slide agglutination test using washed RBCs is already positive, a DAT may not be required.
由於直接抗球蛋白試驗(DAT)通常需要外送檢測,結果往往會延遲,對於疑似免疫介導性溶血性貧血(IMHA)的危急病患,治療應基於臨床懷疑而不應等待檢測結果。可以說,如果使用洗滌紅血球的生理鹽水玻片凝集試驗已呈陽性,可能就不需要進行 DAT 檢測。
Other Testing 其他檢測項目
The degree of confidence in a diagnosis of primary IMHA is largely based on how aggressively causes of nonimmune hemolytic anemia or secondary IMHA have been excluded. Specific tests that may be indicated for selected patients are as follows.
對於原發性 IMHA 診斷的確信程度,主要取決於排除非免疫性溶血性貧血或繼發性 IMHA 病因的徹底程度。針對特定病患可能需要進行的特殊檢測如下。
- Testing for infectious disease
傳染病檢測- Testing of cats for retroviruses (feline leukemia virus, feline immunodeficiency virus)
貓隻逆轉錄病毒檢測(貓白血病病毒、貓免疫缺陷病毒) - Polymerase chain reaction (PCR) testing for Mycoplasma haemofelis (cats), Babesia species (dogs), and, arguably, Mycoplasma haemocanis (dogs). Serologic tests are also available to detect babesiosis in dogs.
聚合酶鏈反應(PCR)檢測:貓血黴漿菌(貓)、巴貝斯蟲屬(犬),以及可爭議性地用於犬血黴漿菌(犬)。血清學檢測也可用於診斷犬隻巴貝斯蟲病。
- Testing of cats for retroviruses (feline leukemia virus, feline immunodeficiency virus)
- Testing for inherited hemolytic anemia
遺傳性溶血性貧血檢測- Genetic testing for pyruvate kinase deficiency and phosphofructokinase deficiency in some affected dog breeds
特定犬種的丙酮酸激酶缺乏症與磷酸果糖激酶缺乏症基因檢測 - Osmotic fragility testing to detect hereditary increases in RBC fragility in affected breeds of cats and dogs. True IMHA, however, can also cause increased RBC osmotic fragility.12
滲透脆性測試,用於檢測貓狗特定品種中遺傳性紅血球脆性增加的情況。然而,真正的免疫介導性溶血性貧血(IMHA)也可能導致紅血球滲透脆性增加。 12
- Genetic testing for pyruvate kinase deficiency and phosphofructokinase deficiency in some affected dog breeds
- Testing for hemostasis
止血功能檢測
- Evaluation of prothrombin time, partial thromboplastin time, D-dimer, and antithrombin if hemolysis is suspected to result from microangiopathic RBC damage and an associated consumptive coagulopathy, particularly in patients for which schistocytes are seen on blood smear
若懷疑溶血是由微血管病變性紅血球損傷及相關消耗性凝血病變引起,特別是血液塗片中發現裂紅血球的患者,應評估凝血酶原時間、部分凝血活酶時間、D-二聚體和抗凝血酶
- Evaluation of prothrombin time, partial thromboplastin time, D-dimer, and antithrombin if hemolysis is suspected to result from microangiopathic RBC damage and an associated consumptive coagulopathy, particularly in patients for which schistocytes are seen on blood smear
- Bone marrow evaluation (aspiration cytology and/or histopathology biopsy)
骨髓評估(抽吸細胞學檢查和/或組織病理學活檢)- Marrow evaluation for patients with suspected IMHA associated with precursor-targeted immune-mediated anemia13,14
對於疑似患有前驅細胞標靶性免疫介導貧血相關 IMHA 患者的骨髓評估 13,14 - Marrow evaluation for patients with unexplained pancytopenia (all 3 major circulating cell lines affected) to rule out concurrent hematopoietic neoplasia, which may induce an immune-mediated anemia
對於原因不明的全血球減少症(所有三種主要循環細胞系受影響)患者進行骨髓評估,以排除可能誘發免疫介導貧血的同時存在造血系統腫瘤
- Marrow evaluation for patients with suspected IMHA associated with precursor-targeted immune-mediated anemia13,14
Final Diagnosis 最終診斷
The American College of Veterinary Internal Medicine (ACVIM) recently published a comprehensive consensus statement regarding the diagnosis of IMHA in dogs and cats.1 Given that all tests can produce false-positive or -negative results for patients with IMHA, the consensus statement suggests a diagnostic algorithm based on multiple test results. The algorithm for an anemic patient categorizes the likelihood of a final diagnosis as diagnostic, supportive of IMHA, suspicious for IMHA, or not IMHA (FIGURE 7).
美國獸醫內科學院(ACVIM)近期發表了一份關於犬貓 IMHA 診斷的全面共識聲明 1 。考慮到所有檢測對 IMHA 患者都可能產生假陽性或假陰性結果,該共識聲明建議基於多項檢測結果制定診斷流程。針對貧血患者的診斷流程將最終診斷可能性分為:確診 IMHA、支持 IMHA 診斷、疑似 IMHA 或非 IMHA(圖 7)。
Definitive: Requires the presence of at least 2 indicators of immune-mediated destruction (positive slide agglutination, positive DAT, or spherocytes) and at least 1 indicator of hemolysis (jaundice/hyperbilirubinemia/marked bilirubinuria, hemoglobinemia/hemoglobinuria, or ghost cells) in the absence of other obvious causes of anemia.
確定性診斷:需符合至少兩項免疫介導性破壞指標(玻片凝集試驗陽性、直接抗球蛋白試驗陽性或球形紅血球)及至少一項溶血指標(黃疸/高膽紅素血症/顯著膽紅素尿、血紅蛋白血症/血紅蛋白尿或幽靈細胞),且排除其他明顯貧血原因。
Supportive: Has several indicators of immune-mediated destruction or hemolysis but does not meet the strict criteria required for a definitive diagnosis.
支持性診斷:具有多項免疫介導性破壞或溶血指標,但未完全符合確定性診斷的嚴格標準。
Suspected: Requires the presence of only 1 indicator of immune-mediated destruction in the absence of indicators of hemolysis.
疑似診斷:僅需存在一項免疫介導性破壞指標且無溶血指標表現。
Another diagnostic clue for dogs and cats that are suspected to have IMHA but do not meet initial criteria for a definitive diagnosis is an appropriate response to immunosuppressive therapy.
對於疑似罹患免疫介導性溶血性貧血(IMHA)但未達初始確定診斷標準的犬貓,另一項診斷線索是對免疫抑制治療呈現適當反應。
IMHA Therapy 免疫介導性溶血性貧血治療
Because IMHA is an immune-mediated disease, treatment has typically been centered on suppressing the immune system and providing supportive care to keep the patient stable until the immune-mediated component of the disease is controlled.
由於 IMHA 是一種免疫介導性疾病,治療通常以抑制免疫系統和提供支持性照護為中心,以維持病患穩定,直到疾病的免疫介導成分得到控制。
Careful initial diagnostic evaluation is needed to ensure that the patient does not have nonimmune hemolytic anemia or IMHA secondary to an underlying trigger such as babesiosis or mycoplasmosis; otherwise, standard therapy will probably be at best ineffective and at worst dangerous.
需要進行仔細的初步診斷評估,以確保病患沒有非免疫性溶血性貧血或由潛在觸發因素(如巴貝斯蟲病或黴漿菌症)引起的繼發性 IMHA;否則,標準治療可能最多無效,最壞情況下甚至可能造成危險。
Glucocorticoids 糖皮質激素
Typically, the cornerstone of IMHA treatment for dogs and cats is glucocorticoids. In fact, for many patients with IMHA, clinical remission can be attained with glucocorticoids alone.
通常,糖皮質激素是治療犬貓免疫介導性溶血性貧血(IMHA)的基石。事實上,許多 IMHA 病患僅使用糖皮質激素即可達到臨床緩解。
For dogs, the standard recommended glucocorticoid therapy is oral prednisone or prednisolone at a starting dose of 2 mg/kg q24h (for large breed dogs, a lower dose of 1 to 1.5 mg/kg q24h or 50 to 60 mg/m2 q24h is suggested). For dogs, no evidence indicates that twice daily dosing with prednisone or prednisolone is any more effective than once daily dosing, and side effects tend to be more pronounced with twice daily dosing.15 Cats typically need, and tolerate, a higher dosage of glucocorticoids; prednisolone (preferable to prednisone in cats) is typically commenced at 2 mg/kg PO q12h. For patients that do not tolerate oral therapy, injectable dexamethasone can be substituted, usually at approximately one-seventh of the calculated prednisone or prednisolone doses.
對於犬隻,標準建議的糖皮質激素治療是口服潑尼松(prednisone)或潑尼松龍(prednisolone),起始劑量為 2 mg/kg q24h(大型犬建議使用較低劑量 1 至 1.5 mg/kg q24h 或 50 至 60 mg/m² q24h)。目前沒有證據顯示對犬隻而言,每日兩次給藥比每日一次更有效,且每日兩次給藥的副作用往往更為明顯。貓咪通常需要且能耐受較高劑量的糖皮質激素;潑尼松龍(對貓而言優於潑尼松)通常以 2 mg/kg PO q12h 開始治療。對於無法耐受口服治療的病患,可改用注射用 dexamethasone,劑量通常約為計算出的潑尼松或潑尼松龍劑量的七分之一。
Recommended glucocorticoid starting doses are typically considered to be immunosuppressive, and such doses are indicated for patients with acute and severe IMHA.
建議的糖皮質激素起始劑量通常被認為具有免疫抑制作用,此類劑量適用於急性且嚴重的 IMHA 病患。
These starting doses, however, are poorly tolerated over the long term and are often associated with numerous unacceptable side effects including polyuria/polydipsia, polyphagia, panting and hyperventilation, muscle weakness and atrophy, hepatomegaly and a pot belly, alopecia, susceptibility to infection (e.g., pyoderma and urinary tract infections), calcinosis cutis, poor wound healing, and increased risk for pulmonary thromboembolism.
然而,這些起始劑量長期使用耐受性不佳,且常伴隨多種難以接受的副作用,包括多尿/多飲、多食、喘氣與過度換氣、肌肉無力與萎縮、肝腫大與腹部膨大、脫毛、易受感染(例如膿皮症與泌尿道感染)、皮膚鈣質沉著症、傷口癒合不良,以及肺栓塞風險增加。
For this reason, although starting doses of glucocorticoids are often effective at treating initial episodes of IMHA, tapering of starting doses should usually begin within a few weeks of commencing therapy.
因此,雖然糖皮質激素的起始劑量通常能有效治療 IMHA 的初期發作,但通常應在開始治療後數週內逐步降低起始劑量。
Other Immunosuppressive Agents
其他免疫抑制劑
Glucocorticoids alone may not be sufficient to control immune disease in patients with severe or refractory IMHA. Even when glucocorticoids are initially effective, unacceptably high doses with associated steroid side effects may be needed to maintain IMHA remission.
對於嚴重或難治性 IMHA 患者,單獨使用糖皮質激素可能不足以控制免疫疾病。即使糖皮質激素初期有效,也可能需要高到難以接受的劑量(伴隨類固醇副作用)才能維持 IMHA 緩解。
In these circumstances, a second immunosuppressive agent is often added to the therapeutic regimen to either increase the chances of initial remission or enable more rapid tapering of glucocorticoid doses for patients experiencing unacceptable steroid side effects.
在這些情況下,通常會在治療方案中添加第二種免疫抑制劑,以提高初始緩解的機會,或讓出現無法接受類固醇副作用的患者能更快減少糖皮質激素的劑量。
A second immunosuppressive agent is much more commonly used in dogs than in cats, probably because cats are more likely to respond to glucocorticoid monotherapy and because they also seem to be less sensitive to steroid side effects.
第二種免疫抑制劑在狗身上的使用頻率遠高於貓,這可能是因為貓對單一糖皮質激素治療的反應較佳,且似乎對類固醇副作用的敏感度也較低。
Many drugs have been used as a second immunosuppressive agent for dogs with IMHA, but strong evidence for efficacy is lacking. The ACVIM recently published a consensus statement regarding the treatment of IMHA in dogs and suggested consideration of azathioprine, mycophenolate mofetil, cyclosporine, or leflunomide as reasonable choices for a second agent.16 Although it is uncommon for cats with IMHA to need therapy beyond glucocorticoids, mycophenolate mofetil, cyclosporine, and leflunomide (but not azathioprine) can all be used in cats with IMHA that is refractory to glucocorticoids.
許多藥物曾被用作治療犬隻 IMHA 的第二種免疫抑制劑,但缺乏強效證據支持其療效。美國獸醫內科學院(ACVIM)最近發表了一份關於犬隻 IMHA 治療的共識聲明,建議可考慮將硫唑嘌呤、黴酚酸酯、環孢素或來氟米特作為第二種藥物的合理選擇。 16 雖然患有 IMHA 的貓很少需要除糖皮質激素以外的治療,但對於對糖皮質激素無效的 IMHA 貓隻,仍可使用黴酚酸酯、環孢素和來氟米特(但不包括硫唑嘌呤)。
Azathioprine 硫唑嘌呤
Azathioprine, a purine synthesis inhibitor that inhibits lymphocyte proliferation, has long been used to treat IMHA in dogs. The recommended starting dose for dogs is 2 mg/kg PO q24h. Azathioprine is usually well tolerated, but a reversible hepatopathy develops in up to 15% of treated dogs.17 For this reason, liver enzymes of dogs receiving azathioprine should be monitored regularly, and azathioprine should be discontinued if the ALT level rapidly rises beyond that expected from glucocorticoids alone. Less common side effects include mild anemia and (rarely) severe neutropenia. Azathioprine is dangerously myelosuppressive in cats; therefore, its use in cats is not recommended.
硫唑嘌呤是一種抑制嘌呤合成並阻斷淋巴細胞增殖的藥物,長期用於治療犬隻的免疫介導性溶血性貧血(IMHA)。建議犬隻的起始劑量為口服每 24 小時 2 毫克/公斤。硫唑嘌呤通常耐受性良好,但高達 15%的接受治療犬隻可能出現可逆性肝病變。 17 因此,應定期監測服用硫唑嘌呤犬隻的肝酶值,若 ALT 數值快速上升超過僅使用糖皮質激素時的預期水平,則應停用硫唑嘌呤。較少見的副作用包括輕度貧血及(罕見的)嚴重中性粒細胞減少症。硫唑嘌呤對貓具有危險的骨髓抑制作用,故不建議用於貓隻。
Mycophenolate Mofetil 黴酚酸酯
Mycophenolate mofetil, another purine synthesis inhibitor, has recently gained popularity for treatment of IMHA in dogs. The recommended starting dose is 8 to 12 mg/kg PO q12h. The most common side effect, which occurs in about 20% of treated dogs, is diarrhea, which can sometimes be severe and is most common at doses higher than the currently recommended starting dose.
黴酚酸酯是另一種嘌呤合成抑制劑,近年來在犬隻 IMHA 治療中日益受到青睞。建議起始劑量為口服每 12 小時 8 至 12 毫克/公斤。最常見的副作用是腹瀉,約 20%的接受治療犬隻會出現此症狀,有時可能相當嚴重,且最常發生於高於目前建議起始劑量的情況下。
Cyclosporine 環孢素
Cyclosporine, a calcineurin inhibitor that inhibits T-cell function, seems to be the most potent immunosuppressive agent standardly available for veterinary use. The recommended starting dose for the treatment of IMHA in dogs is 5 mg/kg PO q12h of the most bioavailable modified (microemulsified) formulation of the drug.
環孢素(一種抑制 T 細胞功能的鈣調磷酸酶抑制劑)似乎是目前獸醫臨床上最強效的標準免疫抑制劑。用於治療犬隻免疫介導性溶血性貧血時,建議起始劑量為每 12 小時口服 5 毫克/公斤,需使用生物利用度最佳的微乳化改良劑型。
Unlike other immunosuppressive agents, cyclosporine has a veterinary-approved formulation, which enables accurate dosing in smaller patients. The most common side effects are nausea and vomiting. Because cyclosporine has unpredictable bioavailability and efficacy, pharmacokinetic or pharmacodynamic therapeutic drug monitoring may be needed to ensure effective dosing.
與其他免疫抑制劑不同,環孢素具有獸醫專用核准劑型,能準確用於體型較小的病患。最常見的副作用為噁心和嘔吐。由於環孢素的生物利用度與藥效具有不可預測性,可能需要進行藥代動力學或藥效學治療藥物監測以確保用藥有效性。
Unlike other immunosuppressive agents, cyclosporine has no marrow suppressive effects, making it the preferred agent for dogs with poorly regenerative IMHA.
環孢素與其他免疫抑制劑不同之處在於不會抑制骨髓功能,因此成為再生不良性免疫介導性溶血性貧血犬隻的首選用藥。
Leflunomide 來氟米特
Leflunomide, a pyrimidine synthesis inhibitor, has not achieved widespread use in veterinary medicine but seems to be well tolerated by most patients. The recommended starting dose is 2 mg/kg PO q24h.
來氟米特(Leflunomide)作為一種嘧啶合成抑制劑,雖未在獸醫領域廣泛使用,但多數病患對其耐受性良好。建議起始劑量為口服每 24 小時 2 毫克/公斤。
Regardless of the immunosuppressive drugs used, it is uncommon for patients with IMHA to respond to therapy in fewer than 5 to 10 days. In the meantime, aggressive supportive measures may be needed to maintain patient stability until immunosuppressive therapy takes effect.
無論使用何種免疫抑制藥物,免疫介導性溶血性貧血(IMHA)病患極少能在 5 至 10 天內出現治療反應。在此期間,可能需要採取積極的支持性措施以維持病患穩定,直到免疫抑制治療發揮作用。
Clinicians should resist the temptation to use higher than recommended drug doses or to use “triple therapy” (3 immunosuppressive agents, including glucocorticoids, concurrently) because such measures are likely to increase the risk for infection without adding therapeutic benefit.18
臨床醫師應避免使用高於建議劑量的藥物或採用「三重療法」(同時使用包括糖皮質激素在內的三種免疫抑制劑),因為此類措施可能增加感染風險卻無額外療效。 18
Transfusion 輸血治療
Many patients with IMHA can tolerate anemia very well; therefore, transfusion is not indicated just because of anemia. Transfusion can, however, be lifesaving for patients with severe anemia (packed cell volume [PCV] <15%), particularly those that show overt clinical signs of anemia such as tachycardia, tachypnea, lethargy, and mental dullness.
許多患有免疫介導性溶血性貧血(IMHA)的病患對貧血具有良好耐受性,因此不應僅因貧血就進行輸血。然而,對於嚴重貧血(血容比[PCV]<15%)且出現明顯臨床症狀(如心搏過速、呼吸急促、嗜睡及精神遲鈍)的病患,輸血可能是挽救生命的關鍵措施。
Transfusion adds more RBCs to a process that already involves excessive consumption of RBCs and therefore carries an associated risk of “fueling the fire.” Transfusion should not, however, be withheld from profoundly anemic patients.
輸血會為本已過度消耗紅血球的病理過程增加更多紅血球,因此存在「火上澆油」的潛在風險。但對於極度貧血的病患,仍不應拒絕給予輸血治療。
For IMHA patients, packed RBC products, which provide RBCs without unnecessary plasma, are preferable to whole blood, although whole blood is acceptable in an emergency. Fresh or recently stored (for fewer than 10 days) products are preferable to long-stored blood products.19,20 Ideally, donor–patient compatibility matching via cross-match or blood typing should be performed before administering transfusion to dogs but may not be possible if autoagglutination interferes with the test method. Fortunately, for dogs, a single first-time unmatched and untyped transfusion is typically safe.
對 IMHA 病患而言,相較於全血,提供純紅血球而不含多餘血漿的濃縮紅血球製品更為理想,但在緊急情況下全血仍可接受。新鮮或近期保存(少於 10 天)的血液製品優於長期儲存的血液製品。 19,20 理想情況下,犬隻輸血前應通過交叉配血或血型鑑定進行供受體相容性匹配,但若自體凝集現象干擾檢測方法則可能無法執行。值得慶幸的是,犬隻首次接受未經配對與血型鑑定的輸血通常具有安全性。
For cats, blood type compatibility should always be verified before administering transfusion, and immunochromatographic typing kits that are not affected by agglutination are available for this species.
對於貓咪,在進行輸血前應始終驗證血型相容性,此物種可使用不受凝集反應影響的免疫層析血型鑑定套組。
The target post-transfusion PCV in dogs with IMHA is about 25% or greater and in cats is about 20% or greater. In very severely affected animals, multiple transfusions (up to 2 transfusions/day) for up to a week or more may be needed to maintain patient stability until immunosuppressive therapy becomes effective.
患有免疫介導性溶血性貧血的犬隻,輸血後目標血容比約為 25%或更高,貓咪則約為 20%或更高。對於病情極度嚴重的動物,可能需要進行多次輸血(最多每日 2 次),持續一週或更長時間,以維持病患穩定,直到免疫抑制治療發揮效果。
Other Therapeutic Options
其他治療選項
For patients with IMHA that is life-threatening and refractory to more standard therapy, other therapeutic options include splenectomy, intravenous human immunoglobulin, liposomal clodronate, and therapeutic plasma exchange.
對於生命垂危且對標準治療無效的免疫介導性溶血性貧血病患,其他治療選項包括脾臟切除術、靜脈注射人類免疫球蛋白、脂質體包覆氯膦酸鹽,以及治療性血漿置換術。
Although each of these more advanced or expensive options certainly seems to benefit some individual IMHA patients, strong evidence to support their routine use is minimal. Some clinicians also recommend oral melatonin as an adjunctive therapy for management of IMHA.
雖然這些更先進或昂貴的治療選項確實對某些個別的 IMHA 病患有益,但支持其常規使用的強力證據仍然有限。有些臨床醫師也建議口服褪黑激素作為 IMHA 管理的輔助療法。
In cats, because IMHA commonly occurs secondary to M. haemofelis infection and because this organism can be hard to identify on blood smears, treatment with doxycycline or pradofloxacin, in addition to glucocorticoids, is often commenced at presentation while confirmatory PCR results are pending.
在貓咪方面,由於 IMHA 常繼發於貓血巴東體(M. haemofelis)感染,且這種病原體在血液抹片中難以辨識,因此除了糖皮質激素外,通常會在確診性 PCR 結果出來前,就開始使用多西環素或普拉多沙星進行治療。
Preventing Pulmonary Thromboembolism During IMHA
預防 IMHA 期間的肺血栓栓塞
In dogs with IMHA, pulmonary thromboembolism is a major cause of death. Therefore, during the initial treatment of IMHA, thromboprophylactic therapy is recommended.16 For first-line therapy, anticoagulant therapy with drugs that inhibit the clotting cascade is recommended, including unfractionated heparin (starting dose 150 to 200 U/kg SC q6h or as a constant rate infusion, ideally with dosing adjustments based on inhibition of factor Xa assay when available), injectable low molecular weight heparins such as enoxaparin (0.8 to 1 mg/kg SC q6h) and dalteparin (150 U/kg SC q8h), or newer oral anticoagulants such as rivaroxaban (0.9 mg/kg PO q24h).
在患有 IMHA 的犬隻中,肺血栓栓塞是主要死亡原因。因此,在 IMHA 的初期治療階段,建議進行血栓預防性治療。 16 作為一線治療,推薦使用抑制凝血級聯反應的抗凝血藥物,包括未分級肝素(起始劑量 150 至 200 U/kg 皮下注射每 6 小時一次或持續靜脈輸注,理想情況下應根據 Xa 因子抑制檢測結果調整劑量)、可注射低分子量肝素如依諾肝素(0.8 至 1 mg/kg 皮下注射每 6 小時一次)和達肝素鈉(150 U/kg 皮下注射每 8 小時一次),或新型口服抗凝血劑如利伐沙班(0.9 mg/kg 口服每日一次)。
Oral antiplatelet agents such as clopidogrel (1 to 4 mg/kg q24h) and low-dose aspirin (1 mg/kg q24h) are less expensive than anticoagulant drugs and are therefore often used.
口服抗血小板藥物如氯吡格雷(1 至 4 mg/kg 每日一次)和低劑量阿司匹林(1 mg/kg 每日一次)價格較抗凝血藥物低廉,因此常被使用。
Prognosis for IMHA IMHA 的預後
Unfortunately, the mortality rate among dogs with IMHA continues to be high (>50%); most deaths occur within the first few months after presentation due to severe anemia, pulmonary thromboembolism, or euthanasia resulting from client intolerance of the high cost of therapy and drug side effects.
不幸的是,患有 IMHA 的犬隻死亡率仍然很高(>50%);大多數死亡發生在就診後最初幾個月內,原因包括嚴重貧血、肺血栓栓塞,或由於客戶無法承受高昂治療費用和藥物副作用而選擇安樂死。
In contrast, the long-term prognosis after survival of the first months of treatment is fair; relapse rates are up to about 20%.21 For most dogs, treatment can be discontinued within 6 to 12 months of presentation, although some require lifelong immunosuppressive therapy. Most cats with IMHA respond well to standard therapy.
相較之下,若能度過治療初期數個月,長期預後狀況尚可;復發率約達 20%。 21 多數犬隻可在就診後 6 至 12 個月內停止治療,但部分病例需終身接受免疫抑制療法。大多數罹患 IMHA 的貓咪對標準治療反應良好。
In recovered IMHA patients, no strong evidence indicates that routine preventive modalities (e.g., vaccination, heartworm prevention, or flea and tick control) will precipitate disease relapses.
對於已康復的 IMHA 病患,目前並無強力證據顯示常規預防措施(如疫苗接種、心絲蟲預防或跳蚤壁蝨防治)會導致疾病復發。
References 參考文獻
1. Garden OA, Kidd L, Mexas AM, et al. ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats. J Vet Intern Med 2019;33(2):313-334.
2. Noble SJ, Armstrong PJ. Bee sting envenomation resulting in secondary immune-mediated hemolytic anemia in two dogs. JAVMA 1999;214(7):1026.
3. Ong HM, Witham A, Kelers K, Boller M. Presumed secondary immune-mediated haemolytic anaemia following elapid snake envenomation and its treatment in four dogs. Aust Vet J 2015;93(9):319-326.
4. Schaefer DMW, Stokol T. Retrospective study of reticulocyte indices as indicators of iron-restricted erythropoiesis in dogs with immune-mediated hemolytic anemia. J Vet Diagnostic Investig
2016;28(3):304-308.
5. Piek CJ, Junius G, Dekker A, et al. Idiopathic immune-mediated hemolytic anemia: treatment outcome and prognostic factors in 149 dogs. J Vet Intern Med 2008;22(2):366-373.
6. Orcutt ES, Lee JA, Bianco D. Immune-mediated hemolytic anemia and severe thrombocytopenia in dogs: 12 cases (2001-2008). J Vet Emerg Crit Care 2010;20(3):338-345.
7. Goggs R, Boag AK, Chan DL. Concurrent immune-mediated haemolytic anaemia and severe thrombocytopenia in 21 dogs. Vet Rec 2008;163(11):323-327.
8. Reimer ME, Troy GC, Warnick LD. Immune-mediated hemolytic anemia: 70 cases (1988-1996). JAAHA 1999;35(5):384-391.
9. Caviezel LL, Raj K, Giger U. Comparison of 4 direct Coombs’ test methods with polyclonal antiglobulins in anemic and nonanemic dogs for in-clinic or laboratory use. J Vet Intern Med 2014;28(2):583-591.
10. Warman SM, Murray JK, Ridyard A, et al. Pattern of Coombs’ test reactivity has diagnostic significance in dogs with immune-mediated haemolytic anaemia. J Small Anim Pract 2008;49(10):525-530.
11. Overmann JA, Sharkey LC, Weiss DJ, Borjesson DL. Performance of 2 microtiter canine Coombs’ tests. Vet Clin Pathol 2007;36(2):179-183.
12. Paes G, Paepe D, Meyer E, et al. The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia. Acta Vet Scand 2013;55(1):74.
13. Stokol T, Blue JT, French TW. Idiopathic pure red cell aplasia and nonregenerative immune-mediated anemia in dogs: 43 cases (1988-1999). JAVMA 2000; 216:1429–1436.
14. Lucidi CD, de Rezende CL, Jutkowitz LA, Scott MA. Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors. Vet Clin Pathol 2017 Sep;46(3):401-415.
15. Swann JW, Szladovits B, Threlfall AJ, et al. Randomised controlled trial of fractionated and unfractionated prednisolone regimens for dogs with immune-mediated haemolytic anaemia. Vet Rec 2019;184(25):771.
16. Swann JW, Garden OA, Fellman CL, et al. ACVIM consensus statement on the treatment of immune-mediated hemolytic anemia in dogs. J Vet Intern Med 2019;33(3):1141-1172.
17. Wallisch K, Trepanier LA. Incidence, timing, and risk factors of azathioprine hepatotoxicosis in dogs. J Vet Intern Med
2015;29(2):513-518.
18. Gregory CR, Kyles AE, Bernsteen L, Mehl M. Results of clinical renal transplantation in 15 dogs using triple drug immunosuppressive therapy. Vet Surg 2006;35(2):105-112.
19. Hann L, Brown DC, King LG, Callan MB. Effect of duration of packed red blood cell storage on morbidity and mortality in dogs after transfusion: 3,095 cases (2001-2010). J Vet Intern Med 2014;28(6):1830-1837.
20. Maglaras CH, Koenig A, Bedard DL, Brainard BM. Retrospective evaluation of the effect of red blood cell product age on occurrence of acute transfusion-related complications in dogs: 210 cases
(2010–2012). J Vet Emerg Crit Care 2017;27(1):108-120.
21. Weingart C, Thielemann D, Kohn B. Primary immune-mediated haemolytic anaemia: a retrospective long-term study in 61 dogs.
Aust Vet J 2019;97(12):483-489.
Quiz 測驗
This article is no longer available for RACE credit but you can still take the quiz for fun!
1. Immune-mediated hemolytic anemia (IMHA) is a good example of which type of immune-mediated reaction?
a. Type I (allergic)
b. Type II (cytotoxic)
c. Type III (immune complex)
d. Type IV (delayed)
2. Which of the following clinical features does not strongly suggest the presence of intravascular hemolysis?
a. Hemoglobinemia
b. Hemoglobinuria
c. Jaundice
d. Ghost cells
3. Which organ is most likely to be damaged by the presence of intravascular hemolysis?
a. Brain
b. Heart
c. Liver
d. Kidney
4. Which of the following infectious diseases has been strongly associated with secondary IMHA
in dogs?
a. Brucellosis
b. Leptospirosis
c. Babesiosis
d. Bartonellosis
5. Evans syndrome should be suspected in IMHA patients that have what abnormality on routine complete blood count evaluation?
a. Marked thrombocytopenia
b. Marked neutrophilia
c. Pancytopenia
d. Schistocytosis
6. Which red blood count abnormality strongly supports a diagnosis of IMHA in dogs?
a. Heinz bodies
b. Eccentrocytes
c. Schistocytes
d. Spherocytes
7. Which of the following immunosuppressive agents has no known marrow suppressive effects?
a. Azathioprine
b. Mycophenolate mofetil
c. Leflunomide
d. Cyclosporine
8. Which of the following immunosuppressive agents is considered to be highly dangerous in cats?
a. Prednisolone
b. Cyclosporine
c. Mycophenolate mofetil
d. Azathioprine
9. Which is the preferred blood product for transfusing dogs with IMHA?
a. Fresh frozen plasma
b. Packed red blood cells that are fresh or have been stored for fewer than 10 days
c. Whole blood that is fresh or has been stored for fewer than 10 days
d. Whole blood that has been stored for more than 10 days
10. Which of the following anticoagulants used to prevent pulmonary thromboembolism can be
given orally?
a. Unfractionated heparin
b. Dalteparin
c. Enoxaparin
d. Rivaroxaban