12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
1202
UTILITY OF THE PFA-100TM FOR SCREENING OF PAEDIATRIC PATIENTS WITH PRIMARY
HAEMOSTATIC DIATHESIS
A. Makis, C. Burgess, A. Rao, K. Khair, R. Liesner
Great Ormond St NHS Trust, LONDON, United Kingdom
Background. The PFA-100TM is a platelet function analyzer, which
uses high shear stress blood flow to simulate primary haemostasis and
assess platelet function. The experience of PFA-100TM use in the paediatric
setting is to date still relatively limited. Aim. Given the large number
of children managed and screened for haemostatic disorders in our
unit we decided to determine the performance of PFA-100TM instrument
as a global test of primary haemostasis. Patients and Methods. We
evaluated the performance of both PFA-100TM cartridges (collagen/ADP
and collagen/Epi) in 365 consecutive children referred with potential
primary haemostatic diathesis. The mean age was 5.7 years, with a
range from one month to 18.2 years (218 boys, 179 girls). At the end of
the study, the PFA-100TM results were compared with the confirmed
diagnosis and analysed for the specificity and the sensitivity. Receiver
operating characteristic curves were used to compare the relationship
between sensitivity and specificity for the two different PFA-100TM
cartridges for all the samples and for each of the patients groups. Results.
Von Willebrand’s disease (VWD) was the commonest haemostatic disorder
(14.3%). Forty-eight children had VWD type 1, one VWD type 2B
and three VWD type 3. Mild platelet defects were diagnosed in 12.6%;
18 had Hermansky Pudlak syndrome, four storage platelet defect and 24
platelet release defect. Severe platelet defects was found in 4.1% of the
children; 14 with Glanzmann’s thrombasthenia and one with Bernard
Soulier’s disease. Thrombocytopenia of various causes was the diagnosis
in 8.2% of the population studied, and treatment with non-steroid
anti-inflammatory drugs in 5.5%. Normal platelet function was found
in 25.8% of the children and a definite diagnosis was not confirmed in
29.5% for several reasons; did not appear for follow-up, were severely
ill or deceased. The specificity of the device was found to be 83%. The
sensitivity was found to be 100% for severe haemostatic disorders such
as VWD type 2B and 3, Glanzmann’s thrombasthenia and Bernard-Soulier’s
disease. A high sensitivity (95.8%) was yielded for VWD type 1, but
the PFA-100TM performed worse (82.6%) for mild storage and release
platelet defects. The ability of the device to predict the absence of a certain
disorder (negative predictive value) was 100% for the severe disorders,
97.5% for VWD type 1 and 90.7% for mild platelet function disorders.
The positive predictive value for a specific defect was low (20-
74.2%). Conclusions: The PFA-100TM, if used appropriately, can play an
important role as a simple and rapid first-line screening test for primary
haemostasis in children. Because of its high negative predictive value in
at least one of the cartridges, it should increase the efficiency of the conventional
diagnostic assessment of potential platelet defects. Future
improvement of the device’s cartridges may help to increase its sensitivity
to mild VWD and platelet function defects.
1203
DEFERIPRONE (DFO) IS AN EFFECTIVE ORAL IRON CHELATOR IN PATIENTS WITH
HEREDITARY HAEMOCHROMATOSIS (HH) FAILING, OR INTOLERANT TO, VENESECTION
OR DESFERRIOXAMINE (DFO) THERAPY
B. Hammer, M. Brazil, D. Galvani, N.M. Butt
Arrowe Park Hospital, UPTON, United Kingdom
Background. Hereditary Haemochromatosis (HH) is an inherited iron
loading disorder associated with excessive iron accumulation and damage
to organs and tissues such as the heart, pancreas, liver, skin and
joints. The commonest method employed for removing iron stores in
patients with HH is by venesection. However, some patients are unable
to tolerate the intensive venesection required to achieve optimal reduction
in iron stores. Those failing venesection are most commonly offered
second-line therapy with desferrioxamine (DFO). This has several toxicities
and requires considerable compliance and lifestyle modifications
which many patients find unacceptable. Deferiprone (DFP) is an oral
iron chelator approved by the European Regulatory Authority in 1999
as second line therapy for transfusional haemochromatosis in patients
with thalasaemia unable to tolerate DFO. It is generally well tolerated
but its major side effect is the idiosyncratic development of agranulocytosis.
There is no literature on the off-license use of DFP to lower iron
stores in patients with HH despite there being a good pharmacobiological
reason to suggest this may be beneficial Aims. To assess the efficacy
and tolerability of DFP in lowering iron stores in patients with HH
failing, or intolerant to, venesection and DFO at our institution. Meth-
440 | haematologica/the hematology journal | 2007; 92(s1)
ods. We retrospectively reviewed clinical outcomes in all patients with
HH at our institution who were treated with DFP to lower iron stores
following failure, or intolerance to, venesection or DFO therapy. Results.
The results are summarised in Table 1. Seven patients with HH (M=6,
F=1) were eligible for inclusion in the study which covered a period
from October 2004 to February 2007. Their average age was 60 years
(range 42-70 years). All but one were homozygous for the C282Y mutation.
The remaining individual (patient 2) was an H63D heterozygote.
The average serum ferritin on commencement of deferiprone was 1718
micrograms/litre (range 633-4929 micrograms/litre). DFP was commenced
up to the recommended dose of 75 milligrams per kilogram per
day, which equated to total daily doses of 0.5 grams-6.0 grams. Doses
were modified according to clinical response and side effects. Serum
ferritin levels were measured every 3 months for up to 12 months. The
average serum ferritin level at 3 months, 6 months, 9 months and 12
months was 1485 (n=6 evaluable patients), 1242 (n=5), 1166 (n=5) and
1067 (n=4) micrograms/litre. This represented an approximate 38%
reduction in ferritin levels with DFP at 12 months. Two patients developed
reversible grade 2 neutropenia which necessitated dose reduction
(patient 3) and discontinuation (patient 7). No infections were noted
during this period. Patient 6 developed abdominal pains and diarrhoea,
opting to discontinue therapy after less than 4 weeks. Conclusions. DFP
appears efficacious at lowering iron stores in patients with HH who fail,
or are intolerant to, venesection or DFO therapy, with low toxicity. Our
observations merit longer follow up and support further large scale studies
to evaluate the safety, efficacy, cost effectiveness and patient quality
of life of using oral DFP as standard second line therapy, following
venesection, in patients with HH.
Table 1.
1204
THE ROLE OF HYPERCOAGULABLE STATE IN PATHOLOGY – STUDY ON A GROUP OF 7500
CASES
M.L.A. Balea, 1 M. Vintila, 2 M. Mihalcioiu, 3 R. Gheorghe, 1 M.I. Balea4 1 Colentina Clonical Hospital, BUCHAREST, Romania; 2 St Pantelimon Clinical
Hospital, BUCHAREST, Romania; 3 NI Geriatry, BUCHAREST, Romania;
4 NIP Prof. Dr. Marius Nasta, BUCHAREST, Romania
The pathogenesis of hypercoagulable state is particularly complex:
from factors concerning the vascular wall up to genetic changes characteristic
of inherited thrombotic disorders. The study we have carried
out attempts to establish the significance of the various entities for the
clinic. Investigating a group of 7500 patients hospitalized in the clinics
of the institute and surveying the pathology induced by hypercoagulable
states, we insisted only on the deep thromboses of the peripheral
veins, thromboses of the central retina vein, the thromboses of the cerebral
vein, renal vein, Budd-Chiari syndrome, disseminated intravascular
coagulation (DIC), small vessels thromboses, the factors occurring in
the arterial pathology being more complex. The conclusions of our study
point out to a 36,26/1000 hospitalised subjects the frequency of the
pathology induced by hypercoagulable states, of which: -Non Hematologic
Malignancy that induced 22,79% of the thrombotic events -Collagen
diseases (SLE, RA, SS): that induced 10,29% of the thrombotic