Case Report: A 19-Years Old Patient with Haemophilia a with High Response Inhibitor Screening and Quantitation and the Bethesda Method

A severe haemophiliac patient, high response inhibitors, 19 years, who was diagnosed at 8 months old and since then he begins to administer factor VIII concentrates. However, a year later after the start of treatment, they were detected inhibitors that behave as high response inhibitors from the start.

He discontinues treatment with Factor VIII concentrate and instead he begins to administer Factor IX concentrate and prothrombin complex as an alternative treatment.

Through his illness, the patient has made significant bleeding at the level of joint and other muscles such as the psoas. It is a bleeding patient at rest up for what is currently administered prophylactically Prothrombin Concentrate 3 times a week.

This case, the comment will be directed towards laboratory diagnosis and its evolution since he was diagnosed in 1994 to date.

From 2013, screening protocols and quantification of both factors and inhibitors were modified in the Specialized Hematology laboratory of Hospital México, due to problems in the sensitivity and specificity of the method and reagents we were using. The results from these patient specific inhibitors are described in the following paragraphs.

Observations

With the experience and current knowledge of the following it is concluded, according to a literature review that was performed (see Table 1):

1) This time period has persisted inhibitor high title, which is evidenced of the study of mixtures which do not clearly show a potentiation by incubating 2 hours at 37 ° C, since the values of the Control Mix and patient give very similar high values.

2) We were shown only on the date of 14.02.2013, there was a real interference Lupic Anticoagulant (LA), which is confirmed by the method of Russel viper venom.

3) The dates high titer inhibitors were reported against factor VIII (from 6 November 2013 to date), both screening and for the Bethesda, aPTT reagent was used with Kaolin activator which is low sensitivity to LA.

4) On November 20, 2015 there was an error in the interpretation and anti factor VIII inhibitors as negative were reported as potentiation at 37 ° C is not evidenced, but rather was interpreted as interference of an LA, which was communicated to the medical and preventive measures cited in paragraph corrections were made.

5) The last date that the sample was processed, on February 1, 2016, the inhibitor against factor VIII did not affect dilution of silica APTT, so the index ROSNER was not affected (<12) and it was not necessary to mount the LA test, according to the request in identifying protocols inhibitors.

6) Factor VIII deficient plasma is currently being used, which contains von Willebrand factor, as recommended by international guidelines quantization factors.

Conclusions

According to an experience as support center Reference Center in our country, we conclude and recommend the following:

1) Registration of haemophiliac patients with high antibody titer is essential as the description of the protocol to be followed in these patients.

2) The behavior of this inhibitor in the screening test of time and temperature dependence, it was decided to directly mount the Bethesda assay, following the recommendations of the literature on when the use of a reagent with low sensitivity to lupus inhibitor.

3) Within the protocol and as far as we can, we will process the purchase for quantification of factor VIII chromogenic by ELISA methodology, as a confirmatory method.