Pregnancy and SCD

1. Pregnancy and SCD

2. Preconception • Hydroxyurea is teratogenic; pregnancy category class D medication. • Iron overload should treated before becoming pregnant • Chelation therapy should cease upon conception. • All patients should be started on 5 mg/day of folic acid • Individuals with chronic hemolysis may require a higher dose.

3. Ante-partum care • Alloimmunization • Evaluated during the first visit, at which time the risk of alloimmunization is high • Re-evaluated at weeks 24–28, and during delivery, if negative at the first visit • Thromboembolism • All hospitalized patients for an acute medical condition require thromboembolism prophylaxis with low molecular-weight or fractionated heparin, unless such treatment is contra-indicated

4. Ante-partum care • Preeclampsia • Low-dose aspirin after 12 weeks' gestation may decrease the risk of preeclampsia, preterm birth, and poor pregnancy outcomes; however increase bleeding and placental abruption.

5. Ante-partum care: Transfusion in pregnancy • There is no consensus on transfusions in pregnancy. • In a meta-analysis of 1291 patients: Blood 2015;126:2424–2435 • Prophylactic transfusions decreased maternal mortality (odds ratio [OR] 0.23) • Vaso-occlusive pain episodes (OR 0.26) • Pulmonary embolism (OR 0.07) • Perinatal mortality (OR 0.43) • Neonatal death (OR 0.2), and preterm birth (OR 0.59) • Low event rates & a variety of transfusion goals

6. Ante-partum care: Transfusion in pregnancy • Only RCT; prophylactic vs on-demand transfusions: N Engl J Med 1988;319:1447–1452 • Lower vaso-occlusive pain crises (relative risk 0.28) • No significant difference in perinatal mortality, intrauterine fetal demise, or neonatal death • Study was underpowered and the rate of events was small.

7. Ante-partum care: Transfusion in pregnancy • Reasonable approach • Prophylactic exchange transfusions, especially in the third trimester, every 3–4 weeks • Chronic organ dysfunction • “History” of acute chest syndrome • Frequent pain crises • A goal hemoglobin of 10 g/dL and HbS <30%

8. Intra-partum • Delivery is recommended at gestational weeks 38–40 • The general medical indications for cesarean section patients are valid in those with SCD • Local-regional anesthesia preferred because it decreases the risk of sickling complications. • If patients undergo cesarean section they should be transfused to a goal hemoglobin of 10 g/dL.

9. Intra-partum • Thromboprophylaxis is recommended - low-molecular-weight heparin, or heparin. • LMWH/heparin should be discontinued 24 hr prior to delivery and recommenced 12 h thereafter.

10. Post-partum • Prophylaxis with LMWH/heparin should be maintained to 6 weeks after cesarean section. • Hydroxyurea should not be used during lactation as the drug passes into breast milk

11. Perioperative management in SCD

12. Preoperative transfusion • Cooperative Study of Sickle Cell Diseases. Blood. 1995;86(10):3676-84. • In 717 patients undergoing surgical procedures • The combined incidence of all sickle cell-related complications postoperatively was significantly lower in those who had preoperative transfusion compared to those who did not have transfusion. • Similar results were demonstrated in individuals with sickle hemoglobin C (HbSC) disease

13. Preoperative transfusion • A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group. N Engl J Med. 1995;333(4):206-13. 403 • Compared the use of simple transfusion with a hemoglobin (Hb) goal of 10 g/dL preoperatively to the use of exchange transfusion to bring the HbS ≤30 percent. • No statistically significant reduction in the incidence of perioperative complications was seen between the two arms of the study

14. Preoperative transfusion • The transfusion alternatives preoperatively in sickle cell disease (TAPS) study: a randomised, controlled, multicentre clinical trial. Lancet. 2013;381(9870):930-8. • Randomized to either no preoperative transfusion or preoperative transfusion • Patients undergoing low risk (e.g., adenoidectomy, inguinal hernia repair) • Medium-risk (e.g., cholecystectomy, joint replacement) procedures • The transfusion goal was to raise the hemoglobin to 10.0 g/dL. • In patients with preoperative hemoglobin levels of 9.0 g/dL or higher, a partial exchange transfusion was done. • The study was closed early due to significantly more complications in the medium-risk, no preoperative transfusion arm than in the medium-risk transfusion arm (10/33 vs. 1/34).

15. Preoperative transfusion • 2014 NIH Expert Panel Report • Strong Recommendation, Moderate-Quality Evidence • Transfuse RBCs to bring the hemoglobin level to 10 g/dL prior to undergoing a surgical procedure involving general anesthesia.

16. Stroke management in SCD

17. HbSS have a high prevalence (4.01%) and incidence (0.61 per 100 patient years) of cerebrovascular accidents • Ischemic strokes have a bimodal distribution, being more common in children and older adults, and lowest in adults aged 20 to 29 years • Risk factors: prior TIA, low steady-state hemoglobin, recent episode of acute chest syndrome (ACS), and elevated systolic blood pressure • Hemorrhagic stroke most frequent in the 20- to 29-year age group. • Risk factors: low steady-state Hb and high leukocyte count

18. Acute focal neurologic deficits differential diagnosis • Acute arterial stroke (ischemic infarct) • Typically obtain an MRI of the brain to distinguish between a stroke and a TIA • Stroke: strong consideration is given for lifelong regular transfusion therapy • TIA: regular blood transfusion therapy only in the presence of other risk factors • Prior TIAs • Abnormal transcranial Doppler ultrasound measurements • Cerebral vasculopathy • Presence of silent cerebral infarcts

19. Acute focal neurologic deficits differential diagnosis • Hemorrhagic stroke • Most common neurologic event in adults with SCD • No etiology for hemorrhagic stroke is identified in most cases • Subarachnoid hemorrhage is the most common etiology • Intracranial aneurysm • No evidence-based approach • Seizures • Hemiplegic migraine

20. Acute focal neurologic deficits differential diagnosis • Posterior reversible encephalopathy syndrome (PRES) • Headache, seizure, visual disorders, and AMS, and supported by imaging findings that show parietal and occipital involvement of the brain, likely resulting from vasogenic edema • Can be associated with ACS • Central sinus venous thrombosis (CSVT) • MRV is the preferred initial imaging

21. Acute care • Labs • CBC, reticulocyte count • Type and cross match, HbS% • Prothrombin time, activated partial thromboplastin time • Basic metabolic profile • Imaging • MRI/MRV preferred (to evaluate for CSVT) • MRI preferred over a brain CT to detect both hemorrhage and cerebral infarct

22. Acute care • Emergent exchange blood transfusion therapy preferred • Or simple transfusion, followed by exchanged transfusion • Subacute care • Repeat the MRI of the brain within 14 to 30 days after initial stroke

23. Long-term care • Secondary prevention • Exchange transfusion preferred (less iron load) • Hydroxyurea • Hematopoietic stem cell transplant (HSCT) for secondary stroke prevention • May be best option in children