**5.3 Results**

Many studies concentrated on SOS without mention of TMA, hence it is not known if TA-TMA was absent or not considered. The efficacy outcomes of these prophylactic studies with danaparoid were usually mainly expressed as outcome survival (OS) and treatment related mortality (TRM). All efficacy and bleeding outcomes are summarised in **Table 9**.


*1 for 1 adult and 103 children no dosing regimen is available.*

#### **Table 8.**

*Dosing regimens used for danaparoid and controls for SOS/TA-TMA prophylaxis.*

*Danaparoid Sodium: A Review of Its Use in Hepatic Thrombotic Disorders DOI: http://dx.doi.org/10.5772/intechopen.103851*


*Dan = danaparoid, (LMW)H = low and unfractionated heparins, MB = major bleeding, nd = no or unclear data, OS = outcome survival, SOS = sinusoidal obstruction syndrome, TA-TMA transplant associated thrombotic microangiopathy, TRM = treatment related mortality, UDCA = urso-deoxycholic acid.*

*1 early and late refer only to TA-TMA <2 weeks or ≥ 4 weeks respectively, and to TRM ≤3 months or 2–5 years respectively, according to the publications with data on either or both.*

*2 nd = no data or in some cases insufficient clarity of data (mortality rate compared in terms of p values or cumulative frequency charts).*

*3 total is for only acute GvHD (grade II–IV) at 3 months.*

*4 total is for acute GvHD (grade II-IV) at 3 months plus chronic GvHD.*

#### **Table 9.**

*Pooled treatment outcomes of SOS/TA-TMA prevention in danaparoid studies.*

Not all parameters were addressed in each of the seven studies therefore % frequency calculations have been corrected by the available data. This indirect comparison suggests that danaparoid reduces SOS/TA-TMA frequency in patients undergoing HSCT at least as well as a LMWH and UDCA with a lower frequency of bleeding at the dosing regimen used. More importantly it appears that danaparoid ± UDCA reduced TRM. Unfortunately the study with a UDCA treatment only control [99] did not provide information on TRM or OS development and for an unexplained reason halved the dose of danaparoid to 1250 U o.d.

#### **5.4 Adverse events**

The frequency of major bleeding events was lowest in patients receiving danaparoid. The development of GvHD was only mentioned in two study reports with grossly disparate results (see **Table 9**) between anticoagulant alone or combined with UDCA. One dalteparin treated subject developed HIT [105] but there is no record of how this was treated. Two danaparoid treated patients developed DIC. Of the 16 patients undergoing allogenic SCT for Adrenoleukodystrophy [108] transient haemolytic anaemia (2), engraftment syndrome (9) and viral reactivation developed all of which improved with specific treatment or supportive care while danaparoid treatment continued.

Of the 5 specifically paediatric studies three [110, 111, 114] reported no post-BMT complications and two [112, 113] reported 27 patients (8.3%) with SOS, TA-TMA or DIC associated with sepsis or engraftment syndrome. All were successfully treated with recombinant thrombomodulin.
