**3.3.1 Hereditary prothrombotic factors**

The most important factors involved in the genetic predisposition to thrombophilia are the factors of the coagulation cascade and in particular their natural inhibitors. It is not clear if genetic defects of fibrinolysis also contribute to the hypercoagulable state. Certain metabolic defects also cause thrombophilia.

### **3.3.1.1 Coagulation factors**

#### 3.3.1.1.1 Fibrinogen (FI)

Pathophysiology and Clinical Aspects of 52 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

dimers can be detected in the circulation. The specificity of these markers is low; however, the negative predictive value of the D-dimer test to correctly exclude DVT is as high as 89% in adult patients with likely DVT compared to 99% in patients who were categorized as unlikely to have DVT.(Wells et al, 2003) In a study on the outcome of TE in children, elevated D-dimer and/or FVIII:C were found in only 67% of the patients; however, elevation of these markers at diagnosis and during follow-up are significantly correlated with persistence or recurrence of TE and/or a post-thrombotic syndrome. (Goldenberg et al, 2004)

Color Doppler ultrasound, conventional and MRI angiography, lineograms and echocardiography are the diagnostic means of imaging the occlusion of vessels. Pulmonary embolism of proximal pulmonary arteries can be visualized by echocardiography and by CT scan; however, the specificity and sensitivity are low in detecting more distal clots. In such cases ventilation and perfusion scintigraphies are the recommended techniques for children.(Babyn et al, 2005) Transcranial Doppler ultrasound is used to assess the risk of stroke in patients with sickle cell disease. All techniques can be regarded as equally specific, sensitive and precise; their application, however, differs with respect to the region of interest, age and therapeutic options. **Table 3** lists the different techniques with respect to their application.

Lineograms CVC related thrombosis Only clots at the tip of the CVC and the

Bilateral venography DVT, SVT Exception: jugular vein, use color

Abbreviations: CVC, central venous catheter, DVT, deep vein thrombosis, SVT, Sinus venous

Assessment of prothrombotic risk factors is by no means suitable for diagnosing TE. It may possibly help to explain unusual manifestations of TE; however, the predictive power concerning outcome, thereby providing a basis for therapeutic and prophylactic decisions is still a matter of ongoing studies and debate. Interpretation of laboratory data is strongly age dependent since normal ranges may differ considerably between newborns, young children

The most important factors involved in the genetic predisposition to thrombophilia are the factors of the coagulation cascade and in particular their natural inhibitors. It is not clear if

DVT, SVT\* Exception: subclavian vein, use venography

distal adjacent vessel wall

Distal clots in PE

Doppler ultrasound conventional or MRI

**Method Indication Limitations**

intracardial thrombus, pulmonary embolism

Table 3. Imaging methods for Thromboembolism in neonates and children.

Echocardiography CVC-related thrombosis,

\* in young infants through the patent fontanella.

**3.3.1 Hereditary prothrombotic factors** 

**3.3 Prothrombotic risk factors** 

Scintigraphy Pulmonary embolism —

**3.2.3 Imaging** 

Color Doppler ultrasound

thrombosis

and adolescents.

In addition to being the final substrate for thrombin, FI is also an acute-phase protein that may lead to acquired thrombophilia and may also contribute to the risk of arterial TE.(Rothwel et al, 2004) Genetic defects causing dysfibrinogenemia associated with thrombophilia are rare.
