Effectiveness of online learning

Sickle cell disease is an inherited autosomal single gene defect associated with hypoxia induced polymerization of Hb S, causing red cell sickling and subsequently vasooclusion which manifests as severe pain known as crisis.

The major finding in this study is that, the Urinary prostacyclin level was found to be very low in pregnant HB SS subjects, as compared to the values in pregnant HB AA subjects.

This finding is not unexpected, as similar findings have been documented in complicated pregnancies such as in patients with eclampsia and pre-eclampsia. In these patients (eclamptic patients) levels of urinary prostacyclin have been documented to

be low.

It was also found that UP in non –pregnant sickle cell anaemia patients was not statistically significantly different from the level in non-pregnant normal subjects, contrary to previous reports. If this is true, it may mean that it is the pregnancy and not the sickle cell condition per se, that makes all the difference in the sickle cell anaemia subjects, though failure of the appropriate adjustment may be related to overall metabolism in SCA.

The level of adjustment expected in pregnancy is indicated by the finding of a 4-fold increase in UP levels in pregnant Hb AA subjects in this study. This adjustment did not occur in pregnant Hb SS subjects in this study

A major finding in eclamptic patients is that there is usually an impaired of plasma volume expansion, and the cause of this impairment has been a subject of debate.

Changes in renal (aldosterone) and pregnancy (progesterone, oestrogen and human placenta lactogen) hormones have been studied with no definite conclusions. The findings of reduced urinary prostacyclin levels however will imply that the vasodilatory effects of prostacyclin will be lost in these complicated pregnancies, therefore there is reduced vascular capacity to accommodate the expected expansion of blood volume. Thus the major pathology may be causes related to decrease in synthesis of prostacyclin.

If pregnant HB SS subjects also have reduced plasma prostacyclin response to pregnancy as has been demonstrated presently, the reported impairment in plasma volume expansion in pregnant HB SS subjects may be related to the pathology resulting in decrease synthesis in prostacyclin.

The cause of the impairment of prostacyclin synthesis in complicated pregnancy, as has been demonstrated in pregnant sicklers will remain a subject for debate. However the synthetic pathway of all prostaglandins start from activation of cell membrane arachidonates. This may mean that pathologies that will result in decrease synthesis should involve cell membrane.

Prostacyclin synthesis is predominantly by the endothelial cells whereas other vasoactive prostaglandins that have opposite effects to prostacyclin, for example thromboxane, are predominantly synthesized by the platelets. The pathway that may result in impairment of prostacyclin synthesis may have to involve the endothelial cells.

Raised plasma levels of homocysteine have been previously shown to damage endothelial cells and may infact result in arterial and venous thrombosis.^65,66 This damage to the endothelial cells may be the initiating factor for unavailability of the primary precursor of prostaglandin on the endothelial cells, i.e arachidonic acid.

Plasma homocysteine is raised only in very few conditions other than inherited hyper-homocysteinaemia. Nutritional lack such as folate and pyridoxine have been shown to significantly affect methionine homocysteine metabolism, with the resultant effect that deficiency of these vitamins may cause an impairment of a reaction pathway that normally results in salvaging of homocysteine back to methionine.

In patients with sickle cell anaemia, the chronic haemolytic state is a condition of increased

constraints in folate availability. As such two situations (sickle cell anaemia and pregnancy), of increased folate demands are in co-existence. Thus these patients may further lack folate.

This may affect the transulphuration pathway where homocysteine that is normally generated from methionine can not be salvaged back to methionine.

In support of this theory is the report of raised plasma level of homocysteine^87,88 in patients with sickle cell anaemia. This may be contributory to the thrombotic state in these patients.

A pregnant sickler is more likely to have a further rise in homocysteine level, which will further impair prostacyclin synthesis. Therefore the expected rise in prostacyclin level in pregnancy may be blunted as presently demonstrated. Further studies may be required to determine plasma homocysteine levels together with prostacyclin levels in pregnant sicklers to further throw more light on this subject.

Haemoglobin of pregnant AA subjects 10.6g/dl is significantly lower than that obtained for HB AA non pregnant subjects, 11.63g/dl/ This is an expected finding in normal pregnancy as has been previously documented by others. (Abudu, Akanmu et al1998)^89. A drop in haemoglobin level was also found in HB SS pregnant subjects compared with non-pregnant HB SS subjects. The mechanism of reduction in haemoglobin concentration during pregnancy may be the same for both pregnant HB AA and HB SS subjects. Viz- haemodilutional anaemia and anaemia due to increased folate and iron demand.

Total white cell count was also noted to be significantly increased in pregnant HB AA subjects compared to those of HB AA non-pregnant subjects. This is also an expected finding⁹⁰. Marked neutrophil leukocytosis has been documented during pregnancy⁹¹ and a further rise may occur during labour. However changes in WBC in pregnant HB SS appears

level of WBC is usually higher than in HB AA non-pregnant subjects, as is documented in this study. Instead of the expected further rise in WBC in pregnant HB SS subjects, this study documented a significant decrease in WBC. We are not aware that this finding has been previously described. Further studies are required to confirm the findings.

Platelet changes were not characteristic, both in HB SS and HB AA pregnant subjects.

Most studies have not reported any remarkable changes in platelet count during normal gestation. However we observed a significant decrease in platelet count in pregnant HB SS compared with the platelet count in non-pregnant HB SS subjects. Further studies are required to confirm the findings.

CONCLUSION

The main finding in this study was that, contrary to the findings in Hb AA subjects, pregnant Hb SS subject did not demonstrate any significant alteration in prostacyclin level when compared to the non-pregnant situation.

RECOMMENDATION

More studies are needed to determine ways of stimulating prostacyclin response in pregnant SS since administration of prostacyclin is associated with diarrhoea. This will produce the much needed vasodilatation and increase plasma volume in pregnant SS subjects.