Methodical and clinical investigations using the platelet function analyzer PFA-100 in dogs
The platelet function analyzer PFA-100 proofs the capillary in vitro bleeding time by the blood flow through a capillary. The membrane at the end of the capillary has a central aperture and is covered with the platelet aggregation inducing substance (collagen/ADP or collagen/epinephrine). The closure time and optional the blood volume flowing out of the capillary until closure of the membrane aperture can be determined.
The aim of the study was the testing of the clinical applicability of the platelet function analyzer PFA-100 in dogs. Blood of clinically normal dogs was measured as reference (collagen/ADP-cartridge: n=136; collagen/epinephrine-cartridge: n=128) and various preanalytic studies were done. Additionally, dogs with different diseases which are known to change the platelet function in humans and/ or dogs were examined. These diseases were the von Willebrand disease (n=2), uraemia (n=10), various hepatopathies (n=9) (n=2: liver cirrhosis due to copper hepatotoxicosis; n=2: hepatosis; n=3: degenerative hepatopathy;
n=1: liver metastases of a tumour; n=1: hepatitis); portosystemic shunts (n=10), leishmaniasis (n=12); acute lymphatic leukaemia (n=7), chronic lymphatic leukaemia (n=4), lymphosarcoma (n=9) and multiple myeloma (n=4). Dogs with hyperfibrinolysis as a result of metastatic carcinomas were tested (n=8). To prove the influence of acetylsalicylic acid on the primary haemostasis of the dog acetylsalicylic acid was given to clinically normal dogs. Acetylsalicylic acid was added to blood samples of healthy dogs as well. 39 samples of 32 dogs with thrombocytopenia (platelet count < 150.000/µl) of various causes and with haematocrit values > 30 % were examined. The specificity of the platelet function analyzer PFA-100 was assessed in dogs with coagulopathies (coumarin intoxication: n=8; haemophilia A: n=3).
Reference range using the collagen/ADP-cartridge was 53 - 98 seconds (median:
73 seconds) for the closure time and 227 - 318 µl (median: 264 µl) for the blood volume. The reference range using the collagen/epinephrine-cartridge was 92 -
>300 seconds (median: 163 seconds) for the closure time, which reaches the maximum of measurement range (300 seconds), and 296 - 720 µl (median: 414 µl) for the blood volume. The reference range of in vivo bleeding time was 60 -
150 seconds for capillary bleeding and 45 - 90 seconds for subaquale bleeding time.
For precision study in series, median variation coefficients of 7.3 % (closure time) and 2.7 % (blood volume), respectively, were found.
Comparing six different collagen/ADP-cartridge-lot numbers neither the closure time (p=0.1548, ANOVA) nor the blood volume (p=0.0921, ANOVA) was significantly different.
The time of sample storage until measurement (0-24 h) did not influence the closure time (p=0.0842, ANOVA) or the blood volume (p=0.0655) using the collagen/ADP-cartridge. Global statistical comparison by Friedman-test revealed clear differences between times for the closure time (p=0.0120) and blood volume (p=0.0061) using the collagen/epinephrine-cartridge. The local comparison with the Wilcoxon-test showed an increase of closure time at 24-h-storage compared to the 1-h-value.
Blood samples of various levels of haematocrit (collagen/ADP-cartridge) showed significant differences. The decrease of the haematocrit from 40 % to 30% resulted in a clear increase of the closure time (p=0.0049, t-test) and the blood volume (p=0.0030, t-test).
Based on the blood samples of thrombocytopenic and healthy dogs platelet number was closer correlated to the closure time (dogs with thrombocytopenia:
r = - 0.5793; total number of dogs: r = - 0.3991), or the blood volume (dogs with thrombocytopenia: r = - 0.5493; total number of dogs: r = - 0.4340) using the collagen/ADP-cartridge in comparison to the collagen/epinephrine-cartridge. In the group of dogs with thrombocytopenias the correlation between the capillary bleeding time or subaquale bleeding time and the results of PFA-100 was closer using the collagen/ADP-cartridge than using the collagen/epinephrine-cartridge.
After in vivo and in vitro application of acetylsalicylic acid the measurements with the collagen/epinephrine-cartridge showed a pronounced increase of closure time and blood volume. With the collagen/ADP-cartridge the increase was less remarkable.
Particularly the results of dogs with uraemia, leishmaniasis and multiple myeloma indicated platelet function disorders. The interpretation of the automated measurements of platelet function was difficult with diseases
showing thrombocytopenia and anemia. The blood samples of dogs with portosystemic shunts were all within the reference range.
The results of dogs with coagulopathies correspond to the median closure time and the median blood volume of the control group.
The platelet function analyzer PFA-100 detected thrombocytopenias, the acetylsalicylic acid induced thrombocytopathia, different thrombocytopathias and the von Willebrand disease. Moreover the platelet function analyzer had a high specificity to disorders of primary haemostasis. However, because of the influence of the haematocrit, its clinical usability is clearly reduced.
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