**1.5.2 Imaging**

The echocardiography or abdominal ultrasound is the most commonly applied diagnostic method to confirm clinical suspicion of TE or to screen babies for clinically silent disease. (Roy et al, 2002) comparing echocardiographic investigations with venograms and reported a sensitivity of 21-43% and specificities ranging from 76-94%. This study concluded that venography is required to accurately diagnose UVC related TE in neonates.

#### **1.5.3 Laboratory**

Initial laboratory work-up in a neonate in whom thrombosis is suspected should include a full blood count as well as a coagulation screening with determination of prothrombin time, thrombin time and activated partial thromboplastin time.

D-dimers are a positive finding in almost all critically ill neonates. Conversely, negative Ddimers are relatively accurate in ruling out thrombosis in most patients, including neonates.

In almost all neonates, platelet numbers decrease after birth. However, a sudden and severe drop in platelet counts should alert the intensivist. The thrombocytopenia remains one of the most sensistive indicators for micro- (in the setting of sepsis) or macro-circulatory thrombosis (Veldman, 2008).

Also it has been recommended that infants who are diagnosed with clinically significant VTE should undergo testing for inherited and acquired thrombophilic traits. (Beardsley, 2007).

#### **1.6 Management**

There are no published randomized controlled trials (RCTs) and no large cohort studies that report on the outcomes of different treatment modalities in the management of neonatal Pathophysiology and Clinical Aspects of 40 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

the first week of life and it is likely that a number of these :events initially develop antenatally. (Monagle et al., 2008; Veldman, 2008). Presenting symptoms and clinical findings are different in neonates and older patients and are influenced by the extent and rapidity of thrombus formation. Neonates usually have a flank mass, hematuria, proteinuria, thrombocytopenia and nonfunction of the involved kidney. (Nathan et al., 2003). Approximately 25% of cases are bilateral and 52-60% are reported to have evidence of extension into the inferior vena caval (IVC). (Monagle et al., 2008). Overall survival following neonatal RVT is generally favorable. Four small cohort studies with variable follow-up reported 81-100% of neonates survived. Clinical sequelae included chronic renal

Thombosis of the inferior vena cava can present with signs resembling obstruction of the renal vein (hematuria and retroperitoneal mass); however, these will occur bilaterally when the inferior vena cava is affected. In addition, the lower limbs may be edematous and, if blood flow is susbstantially impared, the child may be in respiratory distress and may have

Signs of impared liver function, hepatomegaly and splenomegaly should raise the suspicion of portal vein thrombosis (PVT); however, only about 10% of children with PVT develop

The echocardiography or abdominal ultrasound is the most commonly applied diagnostic method to confirm clinical suspicion of TE or to screen babies for clinically silent disease. (Roy et al, 2002) comparing echocardiographic investigations with venograms and reported a sensitivity of 21-43% and specificities ranging from 76-94%. This study concluded that

Initial laboratory work-up in a neonate in whom thrombosis is suspected should include a full blood count as well as a coagulation screening with determination of prothrombin time,

D-dimers are a positive finding in almost all critically ill neonates. Conversely, negative Ddimers are relatively accurate in ruling out thrombosis in most patients, including neonates. In almost all neonates, platelet numbers decrease after birth. However, a sudden and severe drop in platelet counts should alert the intensivist. The thrombocytopenia remains one of the most sensistive indicators for micro- (in the setting of sepsis) or macro-circulatory

Also it has been recommended that infants who are diagnosed with clinically significant VTE should undergo testing for inherited and acquired thrombophilic traits. (Beardsley, 2007).

There are no published randomized controlled trials (RCTs) and no large cohort studies that report on the outcomes of different treatment modalities in the management of neonatal

venography is required to accurately diagnose UVC related TE in neonates.

thrombin time and activated partial thromboplastin time.

impairment and hypertension. (Monagle et al., 2008)

high blood pressure. (Veldman, 2008)

acute clinical symptoms (Veldman, 2008).

**1.5.2 Imaging** 

**1.5.3 Laboratory** 

thrombosis (Veldman, 2008).

**1.6 Management** 

VTE. Valuable and comprehensive evidence-based clinical practice guidelines have been developed by the American College of Chest Physicians (ACCP) on antithrombotic therapy in neonates and children (Monagle et al, 2008). Their recommendations are necessarily based on extrapolation of principles of therapy from adult guidelines, limited clinical information from registries, individual case studies and knowledge of current common clinical practice.

The following is the summary of the recommendations of the ACCP 2008 on Anticoagulation and Trombolytic Therapy for neonates with VTE: We suggest that central venous lines (CVL) or UVCs associated with confirmed thrombosis be removed, if possible, after 3 to 5 days of anticoagulation (Grade 2C).It is a weak recommendation. We suggest either initial anticoagulation, or supportive care with radiologic monitoring (Grade 2C); however, we recommend subsequent anticoagulation if extension of the thrombosis occurs during supportive care (Grade 1B). It is a strong recommendation. We suggest anticoagulation should be with either of the following: (1) LMWH given bid and adjusted to achieve an anti-FXa level of 0.5–1.0 U/mL: or (2) UFH for 3 to 5 days adjusted to achieve an anti-FXa of 0.35 to 0.7 U/mL or a corresponding APTT range, followed by LMWH. We suggest a total duration of anticoagulation of between 6 weeks and 3 months (Grade 2C). We suggest that if either a CVL or a UVC is still in place on completion of therapeutic anticoagulation, a prophylactic dose of LMWH be given to prevent recurrent VTE until such time as the CVL or UVC is removed (Grade 2C). We recommend against thrombolytic therapy for neonatal VTE unless major vessel occlusion is causing critical compromise of organs or limbs (Grade 1B). We suggest that if thrombolysis is required the clinician use tPA and supplement with plasminogen fresh frozen plasma) prior to commencing therapy (Grade 2C). For neonates or children with unilateral renal vein thrombosis (RVT) in the absence of renal impairment or extension into the inferior vena cava, we suggest supportive care with monitoring of the RVT for extension or anticoagulation with UFH/LMWH or LMWH in therapeutic doses; we suggest continuation for 3 months (Grade 2C). For unilateral RVT that extends into the inferior vena cava, we suggest anticoagulation with UFH/LMWH or LMWH for 3 months (Grade 2C). For bilateral RVT with various degrees of renal failure, we suggest anticoagulation with UFH and initial thrombolytic therapy with TPA, followed by anticoagulation with UFH/LMWH (Grade 2C).Remark: LMWH therapy requires careful monitoring in the presence of significant renal impairment.
