Pregnancy and SCD

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.

Ante-partum care Alloimmunization Thromboembolism 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

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.

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

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.

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%

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.

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.

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

Perioperative management in SCD

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

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

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).

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.

Stroke management in SCD

Hemorrhagic stroke most frequent in the 20- to 29-year age group. 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

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

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

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

Acute care Labs Imaging 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

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

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