PE Makris, G Gerotziafas,

E Pithara, Th Papageorgiu,

F Athanasiadu, D Katriu.

Haemostasis & Thrombosis Unit,

AHEPA University Hospital,

Thessaloniki-Greece.

case report

* A boy 2,5 years old, (haemophiliac A, FVIII:C <1%) had received 2000 units of Monoclate-P for a gastrointestinal bleeding.

* 40 days later he had had an hemar­throsis in the left knee and was treated with 1000 units Kogenate. In the same time we decided to implant a infuse-a- port.

On the day of operation (6 days later) he received 1000 units of Kogenate without any haemorragic problem. After 2h, the child started to bleed and another administration of 1000 units didn’t give any result. There was no apparent surgical reason of bleeding.

The general situation of the boy had been aggravated and he received two units of red blood cells and another 2.000 units of Kogenate. On the 2nd day an overdose of 3000 units of Kogenate was without any real haemostatic effect.

The labora­tory control revealed a strong in­hibitor of FVIII:C (256 Bethesda units). Waiting for Novo Seven (kindly offered from Novo Nordisk), we treated with cyclo­phosphamide and Kogenate, but the results were poor.

Furthermore, the surgical field had been in­fected by Pseydomonas and Timentin was administered.

Treat­ment (22/11) with NovoSeven at 1,2 mg every 4 h had poor results. The child was re-operated (25/11) for the removal of the in­fuse-a-port for it was considered as the pos­sible cause of infection

During this operation the patient was covered with 2,4 mg every 3h and only after this dos­age the bleeding definitively stopped.

table I. Laboratory findings.

date       FI     Inhib  A₂-APL  TAT    F₁₊₂         PAP   Di-D  Hct

                     g/l      B/u          %            μg/l nm/l      μg/l μg/l %

19/10     3.9  -           -             10          1.2  300 0.5  33

22/11     6.9  256 122 17  2.2  1200      1.0  -

25/11     4.4  256 `99 70  2.3  950 4.0  30

4/12       2.3  256 108   5.5       1.7  470 1.0  36

comments

In this table we present some laboratory parametrs indicating the activation of hae­mostasis after the Novo-Seven administra­tion, like fI, A₂-APL, TAT, F_1+2,, PAP, Di-D_-

It is obvious that the increased dose of rFVIIa (2,4 mg/kgr) on 25/11 activated tran­siently the coagulation and the fibrinolysis.

conclusion

 The administration of rFVIIa was effective for the treatment of this inhibitor in a very high titer.

Hematuria and

renal colics

in haemophilic patients.

GT Gerotziafas, K. Konstantinidis, G.  Kaiafa, E.Pithara, PE Makris.

Haem. & Throm. Unit,

AHEPA Univ. Hospital Thessaloniki Greece.

In the past, hematuria in haemophilic patients used to be treated by re­placement therapy or by ε-aminocaproic acid -EAKA

As a result, pa­tients could develop transient anuria, calculi formation and gradual dete­rioration of renal function, complications associated with the formation of haemo­globin crystalls inside the kidney.

Later, conservative manage­ment of these epi­sodes, which  included  fluid   replacement  

  and admini­stration of soda, was recom­mended.

These measures not only shortened, but they pro­longed the duration of hematuria for 25-30 days, a fact that leads to ex­cessive blood loss and provokes anxiety to the patient.

Fur­thermore, hema­turia is often accompa­nied. by renal colics (1 patient in 3), even after the ad­ministration of EAKA, re­placement therapy with concetrated fac­tors or without any treatment.

In addition, because of the often infection of haemophiliacs with HIV virus, it is im­perative that the duration of hematuria be short, for the safety of the persons related to the patient.

Material and methods

       We studied

65 episodes of hematuria in 50 pa­tients

        * 46 suffering from haemophilia A and

·                 4 from haemophilia B.

Table.

Comparison among the different treatment procedures.

conclusion

1. Conservative measures.

2. administration of 5-20 iu/Kgr of high purity concentrated factors.

3. tranexamic acid, 500 mg 3 times a day. In this way the duration of hema­turia is only 1-2 days.

Coronary artery by-pass

surgery in an

haemophiliac patient :

continuous infusion

of factor VIII:C concentrate.

Makris PE, Oikonomidis A, Diarmisakis E, Pithara E, Papadopulos K,

GT Gerotziafas, Z Foka, Spirou P.

Haemostasis & Thrombosis Unit

AHEPA University Hospital, 

Cardio-Surgery Clinic

“G Papanikolaou” Hospital

Thessaloniki Greece.

Elevated factor VIII levels are related with coronary artery disease.

Fur­thermore, bolus administration of con­centrated factor is associated with athe-rogenic effect due to its high peak levels.

Continuous infusion is a method which can minimise these side-effects.

Material and methods:

Man 62 years old, weighing 104 kg, had suf­fered from severe haemo­philia A, mitroid valve stenosis with atrial fibrillation and developed atheromatic coronary disease.

As a conse­quence, he underwent surgical opening of the valve and coronary artery "by-pass" surgery of one vesi­cle.

We administered highly pu­rified FVIII (Monoclate -P) according to the follow­ing protocol:

a) 6000 iu bolus in the beginning of the op­era­tion,

b) 12000 iu continu­ous infusion using a pump, during the operation (which had lasted for 4 h),

c) during  the first 24 h 48000 iu. Rate of administra­tion: 2000 iu FVIII:C plus 20 iu of heparin (5 ml/h).

Every 4h we were renewing the solution.

On the second day the dosage was re­duced to 18000 iu,

on the  third day to 6000 iu, from

the fourth till the tenth day to 3000 iu and

on the tenth till the fourteenth day to 500 iu/24h.

Results -comments:

Levels of FVIII:C varied between 95-31%, TAT increased the third day (90μg/ml), while F1+2 remained less than 4 nmol/l.

The patient was successfully treated with this alternative method without any clinical or laboratory complications

Stability of concentrated factors of coagulation

E Pithara, G Gerotziafas,

K Konstantinidis, PE Makris

Haemostasis and Thrombosis Unit,

AHEPA University Hospital,

Thessaloniki, Greece.

In order

to start using the continuous in­fusion of concentrated factors of coagu­lation in the clinical praxis for the replacement therapy of hae­mophilic syndromes,

we checked the stability of these com­pounds after their reconstitution.

We took 500 μl of each compound, which had already been ready for admini­stration, and

we checked its activity at the beginning, and after 30 min 4h and 24 h respectively.

We checked the following commercial preparations: Monoclate-P, Mononine, Coate-H and Kogenate.

Results:

The changes in factor activity observed during the above four time periods didn’t establish the stability of these compounds.

Therefore, we decided to use a new solution every 4 h for the case of replace­ment therapy by continuous infu­sion.

The experiment took place in very high exter­nal temperature (in July).

In September we repeated the experi­ment and realised that all the preparations had re­mained stable for 24 h.

Nevertheless, for security reasons, we recom­mend to change the dilution every 4 h in the case of continuous infusion.