name=keywords>
Portuguese Italian Spanish English French German



   I'll Help You To

  ~ Get focused & on track

  ~ Grow your business

  ~ Stop procrastinating


 I'm an ADD-savvy Business
 Coach for ADD-ish entre-
 preneurs
to make your
 journey to greater success
 and happiness faster, easier
 & a whole lot more fun . . .
  
 The ADD-ish way!

Home

Bio

Cool Stuf to buy!

Articles

 




      
THROMBOSIS IN CHILDREN WITH CANCER

I. ETIOLOGY

A.     Background

Thrombotic events in most children have been associated with at least two of the following factors.

Thrombophilic condition

Malignancy

Presence of a central venous line (CVL)

Total parenteral nutrition (TPN)

Immobility

B.     Children with cancer

Many children with cancer already have two factors associated with increased thrombosis shortly after their diagnosis (i.e., malignancy and the placement of a CVL).

C.     Thrombophilic condition

For a child with a confirmed thrombosis and a family history of thrombosis, consider the following conditions that have been shown to place a patient at increased risk of thrombosis: ATIII deficiency, protein C deficiency, protein S deficiency, nonspecific inhibitor, and anticardiolipin antibody.

The presence of activated protein C cofactor resistance or factor V Leiden mutation may increase the risk of thrombosis.

D.     Malignancy

Certain malignancies have been associated with thrombosis due to the secretion of a thromboplastin-like material activating the coagulation pathway.

Acute promyelocytic leukemia [French-American-British (FAB) classification M3] and other malignancies have been associated with the development of DIC. Micro-thrombi at the level of the capillary bed are well recognized. Occasionally, this condition progresses to such an extent that thrombosis of extremities occurs.

E.     Central venous lines

Prospective screening of patients with CVLs for thrombosis associated with the CVL has shown the incidence to be as high as 35%.

F- Total parenteral nutrition

Endothelial cell damage has been shown in vitro with the use of TPN, and it has been postulated that the high osmolarity is the cause.

G. Immobility

In adults, immobility has been shown to be a risk factor for thrombosis.

II. DIAGNOSIS

A. Clinical

A swollen arm or leg suggests the presence of a deep venous thrombosis (DVT). Consider superficial venous dilatation on the arm or chest of a patient who has had a CVL in the upper venous system to be evidence of thrombosis until proven otherwise.

Acute-onset pleuritic chest pain, unexplained shortness of breath, and decreased oxygen saturation suggest the presence of a pulmonary embolism (especially if the DVT is in an arm or leg or if a CVL is in place). Pulmonary embolism can be a life-threatening emergency. If this diagnosis is a possibility and the patient is extremely symptomatic (tachycardia, hypotension, and hypoxia), initiate treatment immediately.

Unremitting headache, seizures, and change in level of consciousness suggest the presence of a cerebral sinovenous thrombosis (CVT).

B.     Deep vein thrombosis

The gold standard for the diagnosis of an arm or leg thrombosis is a venogram. The contrast dye is injected in the hand of the affected arm or the foot of the affected leg. If there is a filling defect in more than two views of the limb, this is diagnostic for DVT.

Ultrasound (either Doppler or compression) in the leg has been validated in adults to be as sensitive and specific as venography. There has been no validation of ultrasound to diagnose DVT in the arm.

Recommendations

a.     If DVT suspected, perform venography on the affected

limb if possible. If venography is not available, ultra-

sound of the leg may be used.

b.     Ultrasound of the upper venous system may be very

inaccurate and may miss a DVT.

c.     If a DVT/pulmonary embolism is identified, treat the

patient with anticoagulants.

C.     Pulmonary embolus

The gold standard for the diagnosis of a pulmonary embolus (PE) is a pulmonary angiogram. The test used most often is a ventilation perfusion (V/Q) scan. The presence of one segmental mismatch or two or more subsegmental mismatches define a scan as high probability for PE. All other V/Q scans are non high or normal.

Recommendation

When PE is suspected in children, perform a V/Q scan. If the V/Q scan is not high or normal and there is no alternative diagnosis for the respiratory symptoms, perform venography or ultrasound of the legs (a potential source of PE), or if an upper venous system CVL is present, a venogram of the arm with the CVL. If results are negative and respiratory symptoms persist, consider performing a pulmonary angiogram if the patient's condition is stable.

D. Cerebral venous thrombosis

A computed tomographic scan is not sensitive for the diagnosis of CVT.

Recommendation

If CVT is suspected, use traditional angiography or magnetic resonance imaging angiography

III. RECOMMENDATIONS FOR TREATMENT

A.     Heparin

1.     Treatment of children with confirmed DVT/PE:

a.     Loading dose: heparin 75 U/kg IV over 10 minutes

b.     Initial maintenance dose: 28 U/kg/h for infants <1 year, 20 U/kg/h for children >1 year

c.     Adjust heparin to maintain APTT of 60-85 seconds (assuming this reflects an antifactor Xa level of

0.30-0.70).

d.     Obtain blood for APTT 4 hours after administering the heparin loading dose and 4 hours after every change in the infusion rate.

e.     When APTT values are therapeutic, perform a daily CBC and APTT.

2.     Reversal of heparin therapy

a.     If there is bleeding due to heparin that is clinically significant, the anticoagulant effect of heparin may be reversed with protamine sulfate according to dosages maximum dose 50 mg.

b.     The infusion rate of a 10 mg/mL solution should not exceed 5 mg/min.

c.     Hypersensitivity reactions to protamine sulfate may occur in patients with known hypersensitivity reactions to fish or those previously exposed to protamine therapy or protamine-containing insulin.

B.     Low-molecular-weight heparin

1. The following are guidelines for initiating and monitoring enoxaparin therapy. Modifications for individual clinical circumstances may be necessary. The only low-molecular-weight heparin that has been studied in children is enoxaparin (Lovenox, Rhone-Poulenc). Therefore, these dosage guidelines apply to this product only and cannot be directly extrapolated to other low-molecular-weight heparins. The treatment and prophylactic dose of enoxa-

parin in children are extrapolated from adult clinical trials and a cohort study in children.

Consider the use of low-molecular-weight heparins for neonates, any patient requiring anticoagulation and deemed to be at increased risk of hemorrhage, and

Patients for whom venous access for administering and monitoring of standard heparin therapy is difficult.

4. Dosage: enoxaparin (Lovenox has 110 antifactor Xa U/mg).

Avoid aspirin or other antiplatelet drugs during heparin therapy, if possible. If analgesia is required, prescribe acetaminophen.

Avoid intramuscular injections and arterial punctures during anticoagulation.

Measure platelet counts daily. If the platelet count drops below 100 x 109/L, on day 5 or later of initial heparin therapy or any day of heparin therapy if the patient received heparin therapy in the last 3 months, perform a heparin-induced thrombocytopenia (HIT) screen. In adults, the risk of HIT is greater after 5 days of treatment on the first exposure and anytime if the patient has been treated with heparin in the past. The epidemiology of HIT in children has not as yet been established. If a decrease in platelet count occurs and the total count is <100 x 109/L, consider performing a HIT screen.

C. Monitoring low-molecular-weight heparin

In treating a CVL-related thrombosis after the initial 3 months to 1 year of anticoagulant therapy, consider long-term low-dose anticoagulation as thromboprophylaxis if a functional CVL is in place.

On day 1 and/or day 2, draw a blood sample 4 hours after the subcutaneous administration of enoxaparin. If therapeutic, a weekly check on the antifactor Xa level is sufficient (Table 5.6.)

The therapeutic antifactor Xa level for treatment dose therapy is 0.5-1.0 U/mL. The target antifactor Xa level for prophylactic dose therapy is 0.2-0.4 U/mL.

For patients receiving long-term enoxaparin therapy (>3 months), consider bone densitometry studies at baseline and then every 6 months to assess for possible osteoporosis.

If an antidote for enoxaparin is needed, consider the following.

a. If anticoagulation with enoxaparin needs to be discontinued for clinical reasons, termination of the subcutaneous injection will usually suffice. If an immediate effect is required, protamine sulfate has not been shown to completely reverse enoxaparin. Equimolar concentrations of protamine sulfate neutralize the antifactor Ila activity but result in only partial neutralization of the antifactor Xa activity.

b. However, studies in experimental animal models indicate that increased microvascular bleeding produced by very high concentrations of enoxaparin is neutralized by protamine sulfate. The dose of protamine sulfate depends on the dose of enoxaparin used and the time of administration. If protamineIS given within 3-4 hours of the enoxaparin, then a maximal neutralizing dose is 1 mg of protamine per 100 U (1 mg) of enoxaparin given in the last dose.

c. The protamine should be administered intravenously

and over a 10-minute period, as rapid infusion can

cause hypotension.

Newborns may be treated for 10-14 days without the addition of Coumadin.

Based on adult data, a first DVT or PE is treated with anticoagulants for 3 months to 1 year, depending on the extent of thrombosis. If an underlying thrombophilic condition is diagnosed, consider long-term anticoagulation.

E.     Coumadin

Coumadin is an oral anticoagulant used for long-term anticoagulation for some children after heparin or low-molecular-weight heparin is discontinued.

1.     Loading dose

a.     Day 1: if the baseline INR is 1.0-1.3 U/mL, the dose is 0.2

mg/kg PO

b.     Days 2-4.

2.     Maintenance oral anticoagulation dose guidelines.

F.     Thrombolytic therapy

Blocked catheters may be made patent with thrombolytic therapy.

If local thrombolytic therapy for a blocked catheter fails, recommend diagnostic test to rule out CVL-related thrombosis (venography of upper system or ultrasound of lower venous system). If a CVL-related thrombus is confirmed, commence anticoagulation therapy. Consider systemic thrombolytic therapy with anticoagulation.

G.     Thromboprophylaxis for central venous lines

  1. The reported incidence of CVL-related DVT is highly variable, reflecting a spectrum of diagnostic tools (clinical to venography). When objective tests, such as venography, are used, the incidence ranges from 35 to 45%.
  2.      In adults, two studies [Bern et al. (1990) used low-dose

Coumadin and Monreal et al. (1995) used the low-molecu-

lar-weight heparin, Fragmin] demonstrated that prophy-

laxis of CVLs significantly decreases the incidence of

thrombosis.

3.     Side effects of thrombosis in a limb are the following.

a.     Postphlebitic syndrome, consisting of pain, swelling,

and ultimately skin breakdown

b.     Mortality

The Canadian Registry of Pediatric Thrombosis reported 2% mortality associated with thrombosis, usually in the form of PE.

Prophylaxis of CVLs in children is not recommended at this time due to the lack of prospective randomized controlled trials demonstrating safety and efficacy of anticoagulation prophylaxis.

If DVT associated with the placement of a CVL is objectively diagnosed, treatment with anticoagulation is recommended.

H. Cerebral venous thrombosis

Therapy is controversial, but based on an adult study (Einhaupl et al., 1991) anticoagulation for 3 months should be considered.

Note: Carry out thrombophilic blood studies on all children with thrombosis. If abnormal, offer screening of the family for the same abnormality If the abnormality is confirmed, offer high-risk counselling.

*23\168\2*

Cancer

 

 

use this link