Peripartum cardiomyopathy is a form of non-ischemic cardiomyopathy that causes systolic dysfunction in women during the last month of pregnancy or within 5 months post-delivery (Altuwaijri et al., 2012). There are several factors in the coagulation cascade that make the peripartum period hypercoagulable such as increased endogenous thrombin generation, acquired activated protein C resistance, increased levels of coagulation factors VII, VIII, X and plasma fibrinogen, and decreased activated partial thromboplastin time (aPTT) (Hellgren, 2003). These hemostatic changes usually normalize 4-6 weeks after delivery. Additionally, if left ventricular dysfunction persists from PPCM, it leads to blood stasis in the heart making a patient hypercoagulable. In a prospective study from South Africa (n = 100), LV thrombus was found in 16% of the patients with PPCM (Sliwa et al., 2006). In another study by Amos etal (N = 55), 17% of patients developed LV thrombus and none of them had full recovery of LV function (Amos et al., 2006). Kido and Guglin (2019) recently summarized 4 case reports for use of anticoagulation in patient with PPCM with intracardiac thrombi. In our review, we found additional data sources from women with PPCM that developed intracardiac thrombi and received anticoagulation therapy.

Anticoagulation in a patient with PPCM is a topic that lacks extensive medical literature. The guidelines are based on expert opinion and do not delineate clearly the indications for anticoagulation in patients with PPCM. According to the ACCF/AHA guideline in 2013, anticoagulation is recommended for patients with PPCM if ventricular dysfunction is persistent (Writing Committee et al., 2013). However, the terms ''ventricular dysfunction'' and ''persistent'' need to be clearly defined. Recently, the guidelines from the ESC 2018 recommend anticoagulation in women with PPCM with LVEF < 25% (level of evidence IIB) (Seeland et al., 2018).

Studies done by Sheppard et al. (2014) referred to the following as indications for anticoagulation in a patients with PPCM: atrial fibrillation, LV thrombus, systemic embolism, bromocriptine use, and EF less than 30% . All except one patient in our review with intracardiac thrombi had EF < 30%. This finding reiterates the possible need for prophylactic anticoagulation or a closer follow up with serial echocardiograms in patients with low EF. Additionally, all the patients in our review who had LV dimensions measured were found to have large left ventricular end diastolic dimension (LVEDD) and mean of 6.4 cm (range 5.7-6.9 cm). These parameters need to be studied further, and may help categorizing patients with PPCM that might benefit from prophylactic anticoagulation.

Bromocriptine, typically used for lactation suppression, continues to be studied for the treatment of PPCM. In a multicenter randomized study by Hilfiker-Kleiner et al. (2017), bromocriptine treatment was associated with high rate of full LV recovery and low morbidity and mortality in PPCM patients compared to PPCM cohorts that are not treated with bromocriptine. Currently, it is not approved by the US Food and Drug Administration (FDA) for treatment of patients with PPCM, but continues to be investigated. There are few case reports suggesting a prothrombotic effect of bromocriptine like cases of myocardial infarction (Hopp et al., 1996; Loewe and Dragovic, 1998). Due to the prothrombotic effect; however, it is advised to implement a full dose of anticoagulation when bromocriptine is used.

As discussed above, the first 6-8 weeks postpartum have a persistent hypercoagulable state that requires anticoagulation. Both unfractionated heparin and low molecular weight heparin are safe to use during pregnancy because they do not cross the placenta (Gerald et al., 2009). Due to its shorter half-life and reversible effect, unfractionated heparin is preferred during pregnancy whenever an urgent delivery is suspected due to maternal or fetal instability. Warfarin crosses placenta, and is considered a category D drug for use during pregnancy. In postpartum women, neither warfarin nor heparin are secreted into the breast milk and can be offered during breast-feeding (Gerald et al., 2009). The use of novel oral anticoagulants in pregnancy and embryopathy still has significant data gaps. NOACs have not been reported to be used in the setting of PPCM.

The duration of anticoagulation is another ambiguous topic. As per the heart failure guidelines for PPCM, anticoagulation therapy should be continued until LV function normalizes (Johnson-Coyle et al., 2012). In PPCM patients, it has been reported that 23% to 72% achieve full recovery of normal LV systolic function (McNamara et al., 2015). It occurs within 2 to 6 months of diagnosis, but can be delayed for up to 5 years (Fett et al., 2005). In our review, 7 patients had clot resolution within 1 month, 3 patients required a surgical procedure for thrombectomy, and the remaining two patients lacked data on clot resolution.

Since PPCM with intracardiac thrombi is a rare condition, our systematic review only includes case reports. We rely on the information published and cannot conclude certain aspects because they are not included in the study literature.