Spontaneous abortion is one of the most common
complications of pregnancy. Traditionally,
recurrent pregnancy loss has been defined as
the occurrence of 3 or more abortions before
20 weeks. Etiologies of RPL consist of genetic
factors, thrombophilias, anatomic abnormalities,
endocrine abnormalities, maternal infections
and immunologic factors. Even after a
thorough evaluation, however, the potential
cause remains unexplained in about one third
to one half of cases. Immune-mediated RPL has
received more attention than any other single
etiologic reason, nevertheless, techniques for
diagnosis and treatment of most cases remain
The P blood group system which was first reported
by Landsteiner and Levin in 1927 is another
group of carbohydrate antigens controlled
by a specific glycosyl transferase. Its clinical
significance is in rare cases of syphilis and viral
infections and early abortion. The P blood
group consists of 5 phenotypes p1, p2, p1k, p2k
and P as shown in table 1 (
A rare phenotype of system that lacks either
P1 or Pk antigen is denoted as small-p type. The
prevalence of the phenotype has been reported
to be 1/10000-1/100000 (
Properties of respective P-system blood types
|Phenotype||Antigens on RBC||Antibodies in serum||Japanese||Caucasian|
|P1, PK||Anti-P antibody||Rare||Rare|
|PK||Anti- P antibody||Rare||Rare|
|None||Anti-PP1PK antibody||1/10000 -1/100000||1/10000 -1/100000|
The fetus expresses antigens on trophoblastic
tissues as early as 3 weeks (
In this case series study, we report 12 cases with P-blood type of which 11 of them were treated successfully with antibody removal therapy between 2007-2012 in Al Zahra Hospital, Isfahan, Iran. The study was approved by the Department of Ethics at Isfahan University of Medical Sciences.
These patients had history of recurrent pregnancy loss. Anatomic, genetic, endocrine and thrombophilia disorders were excluded in them. Chromosome abnormalities were excluded by parental peripheral blood karyotyping with banding techniques. Anatomic disorders were excluded by hysterosalpingography and to exclude the endocrine and thrombophilia disorders, patients were tested for CBC, diff, Protein S&C, Lupus anticoagulant testing, Anticardiolipin antibody, TSH, T4, Anti TPO, Anti TGB, FBS, GCT, serum homocysteine levels, Anti β2glycoprotein 1, Anti thrombin III, Factor V Leiden, ANA, ANCA and APCA (anti paternal complement antibody). These patients had been assessed for atypical antibodies and anti- P antibody in their serum. For assessing the anti- Pantibody our kit was Biotestcell-P3 (Ref 816017) (Bio-Rad Medical Diagnostics, Germany). The test principle is a hemagglutination test. Anti-p antibody was positive in these patients. Patients were consulted about treatment by plasma exchange and if they became pregnant, intensive prenatal care and plasma exchange was initiated. Written informed consent was obtained from all participants.
Therapeutic plasma exchange was carried out twice a week from early stages of pregnancy (if pregnancy tests were positive) in AL Zahra Hospital. In every course about 900 cc of patient’s blood was taken. Plasma exchange was performed with centrifugation devices used in blood banking procedures and antibodies were separated from blood cells and removed. Then the residual blood was reinfused to the patients. We used normal saline serum and 5 or 20% albumin solution as a substitution fluid. Plasma exchange procedure was performed up to termination of the pregnancy. To evaluate the efficacy of treatment, we monitored fetal development using ultrasonography. Considering the rarity of the maternal blood type and the safety of the fetus, we decided to carry out the scheduled delivery by cesarean.
All calculations were performed with the SPSS Version 16.0 for Windows (SPSS Inc., Chicago, Illinois, USA).
In this study we successfully treated 11from 12 patients with history of unexplained recurrent abortion with plasma exchange. Patient descriptive statistics are presented in table 2. One of the patients did not consent to participate and was excluded. She was a 29 year old woman, who had history of 2 previous spontaneous abortions with no live birth. Her blood group and rh was B positive.
The relative frequency of primary RPL was 83.3% and the relative frequency of secondary RPL was 16.8% in patients. All previous abortions had happened in early stages of pregnancies, specifically in the first trimester. None of the patients had history of blood transfusion. One of the patient’s RH was negative and the other 11 were positive.
All of the p-positive patients treated by plasma exchange had successful pregnancy proceeding to full-term gestational age and healthy newborns. The plasma exchange procedure was performed 59.18 ± 14.1times (range of 20-75 times) on average during the pregnancy. All patients continued plasma exchange up to termination time, except one patient who could not continue the treatment because of far distance to AL Zahra Hospital.
As shown in table 2, three of the newborns (27.3%) weighed below 2500 g but in these newborns the weight was also higher than 2100 g. None of them had anemia or severe jaundice. None required exchange transfusion.
Descriptive statistics of patients
|Age (Y)||Number of gravidities||Number of gbortions||Number of children being born alive||Blood group &Rh||Gestational age at the time of termination (week)||Birth weight of newborn (g)|
|28.45 (4.30)||5 (2-8)||5 (2-8)||0 (0-1)||(O+)||37.54 (0.69)||2729.09 (389.88)|
*Mean (SD) for quantitative variables, Median (Range) and (Mode) for qualitative variables.
Approximately 70% of human pregnancies fail
to achieve viability and an estimated 50% are lost
before the first missed menstrual period. Recurrent
abortion has been defined as the occurrence of 3 or
more clinically recognized pregnancy losses before
20 weeks (
Maternal immune recognition and response undoubtedly
plays an important role in normal pregnancy
and alloimmune disorders may be a cause
of otherwise unexplained recurrent pregnancy loss
(RPL). Alloimmune disorders involve an abnormal
maternal immune response to paternally derived
antigens on embryonic tissues; possibilities
include maternal cytotoxic antibodies, absent maternal
blocking antibodies and disturbance in natural
killer cell function and distribution (
The presence of PP1Pk antibody is considered
a main cause of repeated spontaneous abortion
in early pregnancy and hemolytic disease in new
The timing of the initiating is particularly important
because P and Pk antigens are expressed as
early as 3 weeks of age on the trophoblastic tissues.
Fetal tissue begins to express P1 antigen at
week 19 or later. The anti-P1 antibody is not as
pathogenic as the anti-P and Pk antibodies. The P1
antigen is reported to inhibit expression of P and
Pk antigen (
Some studies suggest that the frequency of plasmaphresis
should be lowered and gradually tapered
at 16 weeks and thereafter. Also in our study
one of the patient who could not continue the treatment
up to term, (plasma exchange performed up
to week 20) had a successful pregnancy and living
child. For the others we continued therapy to
ensure the safety of the fetus because no adverse
effect of plasma exchange was observed, and because
the precise mechanism and the effect of antip
antibody has not yet been elucidated (
More than 70% of newborns weighed more than 2500 g and pathologic intrauterine fetal growth restriction was not detected. No anemia nor severe jaundice was observed and transfusion was unnecessary. So we successfully managed P-incompatibility pregnancies by using plasma exchange.
This is the first study in Iran that tried to evaluate the efficacy of treatment by plasma exchange in patients with rare blood group P. It seems that more studies are needed about the P phenotype.
P-incompatibility is one rare but curable causes of unexplained RPL and early intense antibody removal could be therapeutic. For therapeutic intervention plasma exchange is efficacious and suitable modality.