13. Wabnitz A, Bushnell C. Migraine, cardiovascular disease, and stroke during pregnancy: systematic review of the literature. Cephalalgia 2015; 35:132. 14. Skeith L, Carrier M, Robinson SE, et al. Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis. Blood 2017; 129:934. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 24/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 15. Camargo EC, Feske SK, Singhal AB. Stroke in Pregnancy: An Update. Neurol Clin 2019; 37:131. 16. Camargo EC, Singhal AB. Stroke in Pregnancy: A Multidisciplinary Approach. Obstet Gynecol Clin North Am 2021; 48:75. 17. Hung SK, Lee MS, Lin HY, et al. Impact of Hypertensive Disorders of Pregnancy on the Risk of Stroke Stratified by Subtypes and Follow-Up Time. Stroke 2022; 53:338. 18. Mas JL, Lamy C. Stroke in pregnancy and the puerperium. J Neurol 1998; 245:305. 19. Cauldwell M, Rudd A, Nelson-Piercy C. Management of stroke and pregnancy. Eur Stroke J 2018; 3:227. 20. Kupferminc MJ, Yair D, Bornstein NM, et al. Transient focal neurological deficits during pregnancy in carriers of inherited thrombophilia. Stroke 2000; 31:892. 21. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. 22. De Keyser J, Gdovinov Z, Uyttenboogaart M, et al. Intravenous alteplase for stroke: beyond the guidelines and in particular clinical situations. Stroke 2007; 38:2612. 23. Selim MH, Molina CA. The use of tissue plasminogen-activator in pregnancy: a taboo treatment or a time to think out of the box. Stroke 2013; 44:868. 24. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 25. Activase (alteplase) prescribing information. https://www.accessdata.fda.gov/drugsatfda_do cs/label/2018/103172s5259lbl.pdf (Accessed on October 25, 2021). 26. Murugappan A, Coplin WM, Al-Sadat AN, et al. Thrombolytic therapy of acute ischemic stroke during pregnancy. Neurology 2006; 66:768. 27. Leonhardt G, Gaul C, Nietsch HH, et al. Thrombolytic therapy in pregnancy. J Thromb Thrombolysis 2006; 21:271. 28. Leffert LR, Clancy CR, Bateman BT, et al. Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period. Am J Obstet Gynecol 2016; 214:723.e1. 29. Dicpinigaitis AJ, Sursal T, Morse CA, et al. Endovascular Thrombectomy for Treatment of Acute Ischemic Stroke During Pregnancy and the Early Postpartum Period. Stroke 2021; 52:3796. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 25/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 30. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S. 31. Sibai BM, Caritis SN, Thom E, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 1993; 329:1213. 32. Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet drugs for prevention of pre- eclampsia and its consequences: systematic review. BMJ 2001; 322:329. 33. Jeng JS, Tang SC, Yip PK. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women. Cerebrovasc Dis 2004; 18:290. 34. Silvis SM, Lindgren E, Hiltunen S, et al. Postpartum Period Is a Risk Factor for Cerebral Venous Thrombosis. Stroke 2019; 50:501. 35. Cantu-Brito C, Arauz A, Aburto Y, et al. Cerebrovascular complications during pregnancy and postpartum: clinical and prognosis observations in 240 Hispanic women. Eur J Neurol 2011; 18:819. 36. Skidmore FM, Williams LS, Fradkin KD, et al. Presentation, etiology, and outcome of stroke in pregnancy and puerperium. J Stroke Cerebrovasc Dis 2001; 10:1. 37. Witlin AG, Friedman SA, Egerman RS, et al. Cerebrovascular disorders complicating pregnancy beyond eclampsia. Am J Obstet Gynecol 1997; 176:1139. 38. Liang CC, Chang SD, Lai SL, et al. Stroke complicating pregnancy and the puerperium. Eur J Neurol 2006; 13:1256. 39. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:1158. 40. Bushnell C, McCullough LD, Awad IA, et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:1545. 41. Miller EC, Leffert L. Stroke in Pregnancy: A Focused Update. Anesth Analg 2020; 130:1085. 42. Marshman LA, Aspoas AR, Rai MS, Chawda SJ. The implications of ISAT and ISUIA for the management of cerebral aneurysms during pregnancy. Neurosurg Rev 2007; 30:177. 43. Fox MW, Harms RW, Davis DH. Selected neurologic complications of pregnancy. Mayo Clin Proc 1990; 65:1595. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 26/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 44. Salonen Ros H, Lichtenstein P, Bellocco R, et al. Increased risks of circulatory diseases in late pregnancy and puerperium. Epidemiology 2001; 12:456. 45. Tiel Groenestege AT, Rinkel GJ, van der Bom JG, et al. The risk of aneurysmal subarachnoid hemorrhage during pregnancy, delivery, and the puerperium in the Utrecht population: case-crossover study and standardized incidence ratio estimation. Stroke 2009; 40:1148. 46. Horton JC, Chambers WA, Lyons SL, et al. Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1990; 27:867. 47. Liu XJ, Wang S, Zhao YL, et al. Risk of cerebral arteriovenous malformation rupture during pregnancy and puerperium. Neurology 2014; 82:1798. 48. Gross BA, Du R. Hemorrhage from arteriovenous malformations during pregnancy. Neurosurgery 2012; 71:349. 49. Porras JL, Yang W, Philadelphia E, et al. Hemorrhage Risk of Brain Arteriovenous Malformations During Pregnancy and Puerperium in a North American Cohort. Stroke 2017; 48:1507. 50. Dias MS, Sekhar LN. Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Neurosurgery 1990; 27:855. 51. POOL JL. TREATMENT OF INTRACRANIAL ANEURYSMS DURING PREGNANCY. JAMA 1965; 192:209. 52. Qaiser R, Black P. Neurosurgery in pregnancy. Semin Neurol 2007; 27:476. 53. Tarnaris A, Haliasos N, Watkins LD. Endovascular treatment of ruptured intracranial aneurysms during pregnancy: is this the best way forward? Case report and review of the literature. Clin Neurol Neurosurg 2012; 114:703. 54. Pumar JM, Pardo MI, Carreira JM, et al. Endovascular treatment of an acutely ruptured intracranial aneurysm in pregnancy: report of eight cases. Emerg Radiol 2010; 17:205. 55. Meyers PM, Halbach VV, Malek AM, et al. Endovascular treatment of cerebral artery aneurysms during pregnancy: report of three cases. AJNR Am J Neuroradiol 2000; 21:1306. 56. Piotin M, de Souza Filho CB, Kothimbakam R, Moret J. Endovascular treatment of acutely ruptured intracranial aneurysms in pregnancy. Am J Obstet Gynecol 2001; 185:1261. 57. Davie CA, O'Brien P. Stroke and pregnancy. J Neurol Neurosurg Psychiatry 2008; 79:240. 58. Stoodley MA, Macdonald RL, Weir BK. Pregnancy and intracranial aneurysms. Neurosurg Clin N Am 1998; 9:549. 59. Dashti SR, Spalding AC, Yao TL. Multimodality treatment of a ruptured grade IV posterior fossa arteriovenous malformation in a patient pregnant with twins: case report. J Neurointerv Surg 2012; 4:e21. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 27/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 60. Jermakowicz WJ, Tomycz LD, Ghiassi M, Singer RJ. Use of endovascular embolization to treat a ruptured arteriovenous malformation in a pregnant woman: a case report. J Med Case Rep 2012; 6:113. 61. Martin JN Jr, Thigpen BD, Moore RC, et al. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol 2005; 105:246. 62. McDermott M, Miller EC, Rundek T, et al. Preeclampsia: Association With Posterior Reversible Encephalopathy Syndrome and Stroke. Stroke 2018; 49:524. 63. Singhal AB, Bernstein RA. Postpartum angiopathy and other cerebral vasoconstriction syndromes. Neurocrit Care 2005; 3:91. 64. Bakhru A, Atlas RO. A case of postpartum cerebral angiitis and review of the literature. Arch Gynecol Obstet 2011; 283:663. 65. Fugate JE, Ameriso SF, Ortiz G, et al. Variable presentations of postpartum angiopathy. Stroke 2012; 43:670. 66. Singhal AB. Postpartum angiopathy with reversible posterior leukoencephalopathy. Arch Neurol 2004; 61:411. 67. Fletcher JJ, Kramer AH, Bleck TP, Solenski NJ. Overlapping features of eclampsia and postpartum angiopathy. Neurocrit Care 2009; 11:199. 68. Fugate JE, Wijdicks EF, Parisi JE, et al. Fulminant postpartum cerebral vasoconstriction syndrome. Arch Neurol 2012; 69:111. 69. R mi J, Pfefferkorn T, Fesl G, et al. Uncomplicated pregnancy and delivery after previous severe postpartum cerebral angiopathy. Case Rep Neurol 2011; 3:252. 70. Ursell MR, Marras CL, Farb R, et al. Recurrent intracranial hemorrhage due to postpartum cerebral angiopathy: implications for management. Stroke 1998; 29:1995. 71. Piva I, Scutiero G, Greco P. Amniotic Fluid Embolism: An Update of the Evidence. Med Toxicol Clin Forens Med 2016; 2:2. 72. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e419S. 73. Sibai BM, Coppage KH. Diagnosis and management of women with stroke during pregnancy/postpartum. Clin Perinatol 2004; 31:853. 74. Lamy C, Hamon JB, Coste J, Mas JL. Ischemic stroke in young women: risk of recurrence during subsequent pregnancies. French Study Group on Stroke in Pregnancy. Neurology 2000; 55:269. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 28/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 75. Coppage KH, Hinton AC, Moldenhauer J, et al. Maternal and perinatal outcome in women with a history of stroke. Am J Obstet Gynecol 2004; 190:1331. 76. Cruz-Herranz A, Ill n-Gala I, Mart nez-S nchez P, et al. Recurrence of stroke amongst women of reproductive age: impact of and on subsequent pregnancies. Eur J Neurol 2015; 22:681. 77. Soriano D, Carp H, Seidman DS, et al. Management and outcome of pregnancy in women with thrombophylic disorders and past cerebrovascular events. Acta Obstet Gynecol Scand 2002; 81:204. 78. Mast H, Young WL, Koennecke HC, et al. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 1997; 350:1065. Topic 1108 Version 49.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 29/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate GRAPHICS Causes of stroke or stroke-like events in pregnancy Hematologic Essential thrombocythemia Sickle cell disease Thrombophilias (inherited or acquired) Thrombotic thrombocytopenic purpura Cardiac Valvular abnormalities Arrhythmias, especially atrial fibrillation Cardiomyopathy Infective endocarditis Patent foramen ovale Atrial septal defect Vascular Aneurysms Arteriovenous malformations Vasculopathy (eg, moyamoya disease or syndrome, Takayasu arteritis) Cervical artery dissection Atherosclerotic steno-occlusive cerebrovascular disease Reversible cerebral vasoconstriction syndrome (RCVS) Posterior reversible encephalopathy syndrome (PRES) Cerebral venous thrombosis Pregnancy related disorders Preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome Peripartum cardiomyopathy Amniotic fluid embolism Air embolism caused by caesarean delivery, uterine manipulation, central venous catheterization, or sexual activity Gestational trophoblastic disease https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 30/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Graphic 60303 Version 8.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 31/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Acute stroke differential diagnosis Migraine aura Seizure with postictal paresis (Todd paralysis), aphasia, or neglect Central nervous system tumor or abscess Cerebral venous thrombosis Functional deficit (conversion reaction) Hypertensive encephalopathy Head trauma Mitochondrial disorder (eg, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes or MELAS) Multiple sclerosis Posterior reversible encephalopathy syndrome (PRES) Reversible cerebral vasoconstriction syndromes (RCVS) Spinal cord disorder (eg, compressive myelopathy, spinal dural arteriovenous fistula) Subdural hematoma Syncope Systemic infection Toxic-metabolic disturbance (eg, hypoglycemia, exogenous drug intoxication) Transient global amnesia Viral encephalitis (eg, herpes simplex encephalitis) Wernicke encephalopathy Graphic 69869 Version 7.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 32/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT Evidence of hemorrhage https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 33/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 34/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 35/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Brain MRI of a 33-year-old woman with postpartum angiopathy (reversible cerebral vasoconstriction syndrome) Head MRI axial cuts: FLAIR (A, B, E, F) and apparent diffusion coefficient map (C, D, G, H) sequences. Upper panel MRI, performed on admission, showed FLAIR hyperintensities and diffusion restriction in the right parietal lobe and in the splenium of the corpus callosum (arrows). Lower panel, done on hospital day 3 when the patient deteriorated, showed worsening bilateral lesions involving the cortex and subcortical white matter of the parietal, posterior frontal, and occipital lobes (arrows). MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery. Reproduced with permission from: Maalouf N, Harik SI. Clinical reasoning: A 33-year-old woman with severe postpartum occipital headaches. Neurology 2012; 78:366. Copyright 2012 Lippincott Williams & Wilkins. Graphic 77149 Version 7.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 36/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate CTA showing segmental narrowing of intracranial vessels in a 33 year old woman with postpartum angiopathy (reversible cerebral vasoconstriction syndrome) Head CT angiography (CTA) six days after onset of postpartum occipital headache reveals segmental narrowing of the left middle cerebral artery and the A1 segment of the right anterior cerebral artery (panel A, arrows); in addition, there is segmental narrowing of the posterior cerebral and left distal vertebral arteries with broad narrowing of the basilar artery (panel B, arrows). Head magnetic resonance angiography (MRA) two months after discharge shows complete reversal of arterial pathology (panels C and D). The magnification is similar in all parts of the figure; the white vertical band denotes 5 cm. CT: computed tomography. Reproduced with permission from: Maalouf N, Harik SI. Clinical reasoning: A 33-year-old woman with severepostpartum occipital headaches. Neurology 2012; 78:366. Copyright 2012 Lippincott Williams & Wilkins. Graphic 64318 Version 7.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 37/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate TMA syndromes and other systemic disorders associated with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia Syndrome Clinical features Laboratory findings Primary thrombotic microangiopathy (TMA) syndromes Thrombotic thrombocytopenic May have severe neurologic abnormalities. Severe MAHA and thrombocytopenia; acute kidney injury is rare. purpura (TTP) Inherited; may present in a newborn Severe deficiency of ADAMTS13 infant, a child with thrombocytopenia, or, less (activity <10%). Acquired cases often have a detectable ADAMTS13 commonly, an adult. Among adults, a inhibitor (autoantibody). common presentation is during a first pregnancy. Inherited TTP has ADAMTS13 gene mutation. Acquired autoimmune: Uncommon in children. Complement- mediated TMA Inherited and acquired disorders may present in children or adults. Renal failure is prominent. Inherited disorders usually have a heterozygous mutation in a gene encoding a regulatory protein in the alternate complement pathway (eg, CFH, CFI, CD46/MCP, C3, CFB, CFHRs). Acquired disorder has antibodies to complement factor H or I. Shiga toxin- Abdominal pain; diarrhea (often Renal failure is prominent. Stool may mediated hemolytic uremic bloody); possible history of outbreak or exposure to livestock be positive for the organism (Escherichia coli or Shigella dysenteriae) syndrome (ST- HUS) or contaminated food, although most cases are sporadic. or Shiga toxin. Drug-induced History of exposure to quinine or Immune mediated: Severe acute TMA other implicated medication. kidney injury; drug-dependent Immune-mediated forms have an abrupt onset with fever, chills, antibodies to platelets and/or neutrophils can be demonstrated. abdominal pain, nausea, anuric acute kidney injury. Toxic, dose-related Toxic, dose related: May have gradual or sudden onset of renal failure and hypertension. etiologies may arise gradually, or onset may be sudden with an intravenous toxic agent (eg, Opana- ER). Coagulation- Inherited, typically presents in DGKE, thrombomodulin, or mediated TMA children <1 year old. plasminogen gene mutation. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 38/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Metabolism- Inherited, typically presents in Elevated serum homocysteine and mediated TMA children <1 year old, but may also present in adults. methylmalonic acid, and low methionine levels; increased urinary methyl-malonic acid. MMACHC gene mutation. Systemic disorders that may present with MAHA and thrombocytopenia Disseminated May be caused by infection, Thrombocytopenia, decreased intravascular coagulation (DIC) malignancy, postpartum hemorrhage with hypotension, or a vascular fibrinogen, and elevated D-dimer are typical with acute or chronic DIC. abnormality such as a giant MAHA may occur. Prolongation of the hemangioma (eg, Kasabach-Merritt syndrome). PT and aPTT are seen in acute DIC. Systemic infection May include bacterial, viral, rickettsial, or fungal organisms. High fever and shaking chills are common. Systemic May occur with occult systemic Depends on specific tumor. malignancy malignancy. Breast, prostate, lung, pancreatic, or gastrointestinal tumors are often responsible. Pregnancy-related Typically present in third trimester or Elevated hepatic transaminases. syndromes (eg, severe postpartum. Severe hypertension and liver involvement are often present. Acute kidney injury is uncommon. preeclampsia, HELLP) Abnormalities resolve with delivery. Severe Typically, systolic BP >200 mm Hg and Often associated with severe renal hypertension diastolic BP >100 mm Hg. Neurologic features including PRES may be failure. Renal biopsy demonstrates TMA identical to the primary TMA present. Hypertension may also occur syndromes. in primary TMAs with severe renal involvement, so the temporal relationship is important. Abnormalities resolve with control of the BP. Systemic rheumatic SLE may be associated with hypertension, renal insufficiency, and Serologic testing may show autoantibodies characteristic of the diseases (eg, SLE, autoimmune cytopenias. APS typically underlying condition; APS may have SSc, APS) presents with arterial and/or venous thromboembolism but can also prolonged aPTT. Renal biopsy may demonstrate TMA identical to the produce a TMA. primary TMA syndromes. Hematopoietic cell transplant May occur with autologous or allogeneic transplant. May be No specific findings. associated with exposure to cytotoxic https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 39/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate chemotherapy, radiation, systemic infection, or a calcineurin inhibitor. Solid organ May be associated with calcineurin Renal biopsy may have features of transplant inhibitor administration. May be rejection. associated with infection such as CMV in the setting of immunosuppression. In patients receiving a kidney transplant for a primary TMA syndrome, the syndrome may recur in the transplanted kidney. Therapy for primary TMAs is directed at the underlying pathophysiology; therapy for other systemic disorders associated with MAHA and thrombocytopenia is focused on the underlying disorder. Refer to UpToDate topics on evaluating patients with suspected TMA and on specific syndromes for additional information on presentation/diagnosis and management. TMA: thrombotic microangiopathy; ADAMTS13: A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13; DGKE: diacylglycerol kinase epsilon; HELLP: hemolysis, elevated liver function tests, and low platelets; BP: blood pressure; PRES: posterior reversible encephalopathy; SLE: systemic lupus erythematosus; SSc: systemic sclerosis (scleroderma); APS: antiphospholipid syndrome; CMV: cytomegalovirus; PT: prothrombin time; aPTT: activated partial thromboplastin time. Modi ed from: George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Eng J Med 2014; 371:654. Graphic 100722 Version 5.0 https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 40/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Contributor Disclosures Susan Hickenbottom, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Men-Jean Lee, MD No relevant financial relationship(s) with ineligible companies to disclose. Jos Biller, MD, FACP, FAAN, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Charles J Lockwood, MD, MHCM No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 41/41