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血栓性疾病在犬隻中常見，且對健康造成重大威脅。研究顯示，血漿D-二聚體測試可有效辨識犬隻是否存在血栓形成的風險，尤其在缺乏傳統檢測方法的明確結果時。雖然此測試尚處於早期研究階段，但D-二聚體濃度較高的犬隻，往往與血栓性疾病的發展有關，提供獸醫師一個有用的早期警示工具。
The Use of Plasma D-Dimer Assays to Detect Thromboembolic Disease in the Dog
使用血漿 D-二聚體檢測犬類血栓栓塞性疾病
Andreasen CB, Nelson OL. The use of a plasma D-dimer assay to detect thromboembolic disease in the dog.
Proceedings of the X International Symposium of Veterinary Laboratory Diagnosticians. July 2001. Salsomaggiore,
Italy. Pp. 217-218.
Thrombi that form in the arterial or venous system commonly cause significant morbidity and mortality in human and veterinary patients. Greater than 60% of patients with thromboembolic disease die from this disorder. Procedures for early detection of excessive clot formation are not well defined. Traditional diagnostic methods of contrast angiography, nuclear scintigraphy, and laboratory assays of coagulation can be inconclusive or insensitive in diagnosing thromboembolic disease. Of the laboratory markers, D-dimer has shown clinical utility in early embolism detection for human beings.
In pathologic conditions, plasmin cleaves fibrinogen to yield fragments X,Y,D, and E that are further cleaved to [fibrin(ogen) degradation products (FDPs)] consisting of fragments E and D. Additionally, fibrin polymers are cleaved to produce X oligomers that are further cleaved by plasmin to produce D-dimers. In contrast to the general end product of fibrin degradation (FDPs), the measurement of D-dimer concentrations is indicative of active coagulation (thrombin generation), fibrinolysis (plasmin generation), and D-dimer clearance.
Even though veterinary laboratories are performing D-dimer assays, the reference intervals for clinically healthy dogs, clinically ill dogs without thromboembolic disease, and dogs with known thromboembolic disease are just now being established. Other studies examining D-dimer and FDP testing in dogs with disseminated intravascular coagulation (DIC) compared to healthy dogs found that D-dimers were positive in dogs with fulminate or hemorrhagic DIC. Also, sensitivity, specificity, and predictive values are unknown and often laboratories only report positive or negative results. We found that a positive result without a reported D-dimer concentration is very nonspecific.
We have established D-dimer reference intervals in clinically healthy dogs; D-dimer concentrations in a population of clinically ill dogs without thromboembolic disease; and D-dimer concentrations in a population of dogs known to have thromboembolic disease.
D-dimer determinations are performed in duplicate using a latex agglutination with plasma. Semi-quantitative D-dimer concentrations (<250, 250-500, 500-1000, 1000-2000, and >2000 ng/ml) are determined using undiluted and diluted plasma at 1:2, 1:4, 1:8. We found plasma D-dimer concentrations in healthy dogs were <250 ng/ml (classified as negative). D-dimer concentrations in a population of clinically ill dogs without thromboembolic complications were: Neoplasia: <250 ng/ml = 58%; >250 – 2000 ng/ml = 42%; Heart failure: <250 ng/ml = 86%, 500 – 1000 ng/ml = 14%; Liver disease: <250 ng/ml = 30%, >250 – 2000 ng/ml = 70%; Renal failure: <250 ng/ml = 50%, 250 – 500 ng/ml = 50%; Post-operative: <250 ng/ml = 70%; >250 – 1000 ng/ml = 30%. (Table 1) Dogs with D-dimers = 1000 – 2000 ng/ml had hemoperitoneum or thromboembolic disease (Table 1).
All dogs with thromboembolic disease had strong positive D-dimer concentrations: 1000 – 2000 ng/ml, n = 6; and >2000 ng/ml, n = 3. (Table 1) None of the thromboembolic disease dogs had concurrent elevated FDPs. Even though these results are preliminary and cases are still being accumulated, a positive D-dimer test does not appear to be specific for pathologic thromboembolic disease. This is similar to findings in human beings where Ddimers were elevated in a number of diseases that can be associated with fibrinolysis. In human beings, specificity for deep vein thrombosis and pulmonary thromboembolism is reported as 35%-71%.
In dogs, D-dimer concentrations >2000 ng/ml were consistent with thromboembolic disease, and have continued to be so in more recently evaluated cases. In the absence of a fibrin forming condition, such as hemoperitoneum, titers >1000 ng/ml also indicated a predisposition to thromboembolic disease. FDPs were not abnormal in any group; therefore, FDPs may be an insensitive indicator of thromboembolism that has not progressed yet to DIC.
Sample submission: The sample needed is plasma. Blood is collected into citrate tubes, the tubes centrifuged, and the plasma removed within 30 minutes. Plasma may be sent on ice packs or frozen and sent to the laboratory for analysis. Plasma from heparin or EDTA tubes may be used, but has not been validated in our laboratory for dogs. More information is at http://vetmed.iastate.edu/vpath/diagnostic-services/clinical-pathology
血栓在動脈或靜脈系統中形成，通常會對人類及獸醫病患造成顯著的病痛和死亡率。超過60%的血栓栓塞性疾病患者死於此疾病。過早檢測過多血塊形成的程序尚不明確。傳統的診斷方法，如造影、核醫學掃描和凝血實驗室檢查，對於診斷血栓栓塞性疾病可能結果不明確或缺乏敏感性。在實驗室標記物中，D-二聚體已在早期栓塞檢測中顯示出臨床實用性。病理條件下，纖溶酶會將纖維蛋白原切割產生碎片X、Y、D和E，這些碎片進一步切割成纖維蛋白(原)降解產物（FDPs），由碎片E和D組成。此外，纖維蛋白聚合物會被切割產生X寡聚物，這些寡聚物會被纖溶酶進一步切割，產生D-二聚體。與纖維蛋白降解的一般終產物（FDPs）不同，D-二聚體濃度的測量顯示出活躍的凝血（凝血酶生成）、纖溶作用（纖溶酶生成）及D-二聚體清除。儘管獸醫實驗室也在進行D-二聚體檢測，但臨床健康犬、無血栓栓塞性疾病的臨床病犬及已知有血栓栓塞性疾病的犬隻的參考區間尚在建立中。
其他研究發現，在有播散性血管內凝血（DIC）的狗與健康狗進行D-二聚體和FDP測試時，D-二聚體在急性或出血性DIC的狗中為陽性。此外，敏感性、特異性和預測值尚不明確，且實驗室通常只報告陽性或陰性結果。我們發現，若結果為陽性但未報告D-二聚體濃度，則此結果極為不特異。
我們已經建立了臨床健康犬隻的D-二聚體參考區間；無血栓栓塞性疾病的臨床病犬的D-二聚體濃度；以及已知有血栓栓塞性疾病的犬隻的D-二聚體濃度。D-二聚體測定是通過乳膠凝集法與血漿進行重複檢測。使用未稀釋和1:2、1:4、1:8稀釋的血漿，分別確定半定量D-二聚體濃度（<250、250-500、500-1000、1000-2000和>2000 ng/ml）。
我們發現，健康犬的血漿D-二聚體濃度為<250 ng/ml（分類為陰性）。無血栓栓塞性併發症的臨床病犬的D-二聚體濃度如下：腫瘤：<250 ng/ml = 58%；>250 – 2000 ng/ml = 42%；心臟衰竭：<250 ng/ml = 86%，500 – 1000 ng/ml = 14%；肝病：<250 ng/ml = 30%，>250 – 2000 ng/ml = 70%；腎衰竭：<250 ng/ml = 50%，250 – 500 ng/ml = 50%；術後：<250 ng/ml = 70%；>250 – 1000 ng/ml = 30%。（表1）D-二聚體濃度為1000 – 2000 ng/ml的狗有腹腔積血或血栓栓塞性疾病（表1）。所有患有血栓栓塞性疾病的狗均顯示強陽性D-二聚體濃度：1000 – 2000 ng/ml，n = 6；>2000 ng/ml，n = 3。（表1）所有血栓栓塞性疾病的狗均未同時出現FDP升高。
儘管這些結果仍為初步，且病例仍在累積中，但D-二聚體檢測結果呈陽性似乎並不特異於病理性血栓栓塞性疾病。這與人類的發現相似，在多種與纖溶作用相關的疾病中，D-二聚體升高。在人類中，深靜脈血栓形成和肺栓塞的特異性報告為35%-71%。在狗隻中，D-二聚體濃度>2000 ng/ml與血栓栓塞性疾病一致，且在最近評估的病例中繼續如此。若無形成纖維蛋白的病理條件（如腹腔積血），D-二聚體濃度>1000 ng/ml亦顯示出血栓栓塞性疾病的傾向。在任何組別中，FDP均未異常，因此FDP可能是對未進展為DIC的血栓栓塞性疾病的敏感性不足的指標。
樣本提交：所需樣本為血漿。血液需收集於檸檬酸管中，經過離心後在30分鐘內取出血漿。血漿可放置冰袋中或冷凍送往實驗室分析。來自肝素或EDTA管的血漿可使用，但尚未在我們的實驗室進行狗隻的驗證。更多信息請參見 此網站。
表1：正常、臨床病和血栓栓塞（TE）組別的D-二聚體結果。