Thrombo embolic problems is one of the major complications of neonatal ICU admissions

1. BY
DR:OSAMA ABOU ELFOTOH
Pediatric department Benha
Faculty of medicine.

8. INCIDENCE

9. Clinical studies report incidences from 13% up to 30% (Tanke et
al 1994; Roy et al 2002)
Most recent in Australian guideline of thromboembolism in
neonates 3 August 2020 the incidence is 6.8/1000
Autopsy findings report UVC-related TE in 20% to 65%
(Tanke et al 1994; Khilnani et al 1991; Schmidt and
Zipursky 1984)

10. PHYSEOLOGICAL ASPECT

11. Physiologic aspect of hemostasis:
Thrombin converts fibrinogen into fibrin clot.
Inhibitors of coagulation:
Antithrombin; protein C ;protein S and tissue factor
pathway inhibitors.
Antithrombin activity is potentiated by heparin.

12. Plasmin :
the primary fibrinolytic enzyme degrading fibrin
into fibrindegradiation products and D dimers
plasminogen is converted into Plasmin by tissue
plasminogen activators

13.  Both thrombogecic and fibrinolysis pathways are
altered in neonates .
The fetus and newborn are more susceptible to
thrombosis because of deficiency of thrombin
inhibition and relatively deficient thrombolysis.
(plasminogen, anti-thrombin and protein C may be
extremely low).

14. The infant is protected from thrombosis by physiologic
depression of factors II, VII, IX and X .
But the balance favors thrombin formation over
inhibition especially in the sick neonate.

15. RISK FACTORS

16.  Presence of indwelling vascular catheters is the
greatest risk factor.
Neonatal: infection, dehydration, polycythaemia
(Hct>55%), fluctuations in blood pressure, hypoxia.
infusion of hyperosmolar solutions especially
parenteral nutrition,
low flow of infusion fluid
presence of calcium in the infusate

18. • Fibrin sheaths formed around catheter tip
serve as nidus for bacterial growth
• Inflammation from infection activates
coagulation promoting thrombin formation on
indwelling catheters

19. SITES OF THROMBOSIS

20.  1-Umblical venous catheter.
 2-Umbilical artery catheter.
 3-CVL.
 4-PICC
 5-Peripheral arterial line(PAL)
 6-Even peripheral cannulas.

21. HOW CAN YOU SUSPECT THROMBOSIS
CLINICALLY?

22.  Difficulty in infusing through or withdrawing from
the line.(malfunction of the line)
 Onset of thrombocytopenia in the presence of
intravascular line rises the suscepetion of
thrombosis.

24. UVC thrombosis
Persistent +ve blood cultures from catheter,
thrombocytopenia, line dysfunction
Bilateral lower limb edema with IVC thrombus
Dilated superficial vines of lower limb

25. UAC thrombosis
Aortic and renal arterial involvement
Lower limb ischemia, impaired renal
function, hypertension, congestive
heart failure and NEC

26. PICC lines/ long lines and CVL
Depends on device location and size
Upper venous system thrombosis SVC syndrome
(swelling, pain, discoloration of upper limbs,
chylothorax, chylopericardium)

27. Right atrial placement- intracardiac
thrombus (new onset murmur,
unresolving sepsis,
thrombocytopenia, heart failure) and
embolic complications

28. Peripheral arterial line (PAL)
Limb oedema, pallor or cold extremities distal to
cannulation site, weak/ absent pulse, reduced or
immeasurable BP

29. COMPILICATIONS OF INTRA VASULAR
ACCESS THROMOSIS.

30. 
Short term complications of venous catheter:
loss of access
Pulmonary embolism
specific organ Impairment.
 Acute complications of arterial catheter related
thrombosis :
 renal hypertension.
 NEC.
Peripheral gangrene or other organ failure.

31. hematuria.
intermittent lower extremities perfusion or color
changes.
Fatal pulmonary embolism (PE) occurs
secondary to CVL-related thrombosis

32. IMAGE STUDIES FOR DIAGNOSIS OF
INTRAVASULAR ACCESS THROMBOSIS

33. UVC
Doppler USG (DUSG- safest and widely used)
Venogram (gold standard), MR venogram (in pelvic
and intra-abdominal venous thrombus
UAC
DUSG (preferred)
Contrast angiography (gold standard)
PICC and CVL
CXR, and echocardiography

34. PREVENTION OF INTRAVASCULAR
ACCESS THROMBOSIS

35.  Currently, UFH(unfractionatd heparin) is used to
prolong IVL patency in most newborns either in
the form of flushes with UFH-containing
solutions, or low dose infusions (1 to 3
units/ml/hr).
 Intravascular lines should not be left in place for
longer than 14 days.

36. TREATMENT OF INTRAVASCULAR
ACCESS THROMBOSIS

37. CVLs or UVCs with confirmed thrombosis should be
removed after 3-5 days of therapeutic anticoagulation.
Radiologic monitoring for extension of thrombosis.
If extension occurs, start anticoagulation
No thrombolysis unless critical compromise of organ or
limb

38.  UFH are still widely used to prevent and treat TE
(Kumar et al 2004
 LMWH is increasingly used in NICU in the post-
acute treatment of venous and arterial TE
(Malowany et al 2007).


39. Loading and maintenance dose according
to gestational age:
 < 28-weeks* 25 u/kg 15 u/kg/hour
 28-37 weeks* 50 u/kg 15-20 u/kg/hour
 > 37-weeks* 100 u/kg 28 u/kg/hour
Loading dose over 10 minutes

40.  Bleeding (1.9%):
 Stop infusion – Start protamine if Anti-Factor Xa
level > 0.8 u/mL or large overdose given
 Heparin-induced thrombocytopenia (very rare):
 Drop in platelet count by 50% or persistently <
70-100,000/mm3 occurring 5- 10 days after first
exposure to heparin .

 osteopenia occur with prolonged use

41. LMWH
Dose:
< 28-weeks 1.25 mg/kg SQ q 12-
hours
28-37-weeks 1.5 mg/kg SQ q 12-
hours
> 37-weeks 1.625 mg/kg SQ q 12-
hours

42. Duration of treatment
These agents are stopped either after a few days or
when revascularization has been achieved (as
determined clinically or via imaging). Anticoagulation
used for a short course (10-14 days)
LMWH is increasingly used in therapeutic
concentrations for prolonged therapies of 6 weeks or
even up to 3 months (Agnelli and Becattini
2008; Hull et al 2006)

43. THROMBOLYSIS

44. rtPA (recombinant tissue plasminogen activator)
Gestational Age < 28-weeks dose 0.03 mg/kg/hour
or 0.06 mg/kg/hour
gestational age ≥ 28-weeks As above 0.1-
0.5mg/kg/hour
for 6-12 hours
May repeat daily for 3-days
Efficacy was reported to be 59%–100%.

45. Administration of fresh frozen plasma (FFP) prior to
utilization of thrombolytics may increase success
rates by providing sufficient plasminogen levels.
Frequent monitoring of fibrinogen levels and FFP
administration if fibrinogen levels fall below 100 mg/dl
are required. .

46. Catheter-directed thrombolysis
Catheter-directed thrombolysis (CDT) has been
reported in neonatal period ( Ryan and Andrew
1992; Wang et al 2003).
In these reports, rtPA (dosage 0.01–0.1–0.5 mg/kg/h
[min–median–max]) was used .

47. Surgical
Surgical clot removal and vessel reconstruction may
become necessary in the rare event of life or limb
threatening arterial thromboembolism and in the
even rarer event of massive venous thrombosis.
(Coombs et al 2006)

48. Follow-up
Most clinicians would agree not to treat catheter-
induced thrombosis in a patient without congenital
thrombophilia with long-term anticoagulation.
(Heller and Nowak-Gottl 2003)

49.  • Absolute :
 CNS surgery or ischemia (including birth asphyxia)
within ten days.
 Active bleeding.
 Invasive procedures within three days.
 Seizures within 48-hours
 Relative:
 Platelet count < 50 x 104/microliter (100 x
104/microliter for ill neonates) .
 Fibrinogen concentration < 100mg/dL.
 Hypertension

50.  THANK YOU

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56. Is the arterial line necessary?
If no, remove it!
UACs-warm contralateral extremity •
After removal of UAC or PAL, may have
persistent vasospasm or small clots in distal
end arteries
Topical nitroglycerin:
4-mm/kg dose of 2% ointment (0.2-0.5 mcg/kg)
• Potential side effect – Hypotension

57. • Loading dose over 10 minutes .
Maintain an anti-Factor Xa level of 0.3 – 0.7 units/ml
(PTT of 60-85 s)
• Check anti-Factor Xa level 4 hours after loading
dose and 4 hours after each change in infusion rate
• ± antithrombin activity level

58. The major potential risk of antithrombotic therapy, especially in neonates, is a
hemorrhagic event that is potentially massive and life threatening, in particular
intracranial hemorrhage.

59.  thromboembolic events: conventional
anticoagulation with age-appropriate doses
for a short course (10-14 days)

60.  enoxaparin, the most commonly used LMWH in
newborns, the dose is 1.5 mg/kg subcutaneously
twice daily.

61.  Ahmed a premature male neonate 32 weeks
gestational age and 2 weeks postnatal age
treated in our unit from RDS
 CVL was inserted on rt side on doing echo a
rt atrial thrmbus was attached to the tip of the
CVL so many questions jumb to our mind :
 What to do ? Is it amust that we have to
remove the line ? What the fate of the
thromus if the line is removed ?do we need
anticoagulant or throbolytic therpy and what
else,,,,,,,,,

62.  Thrombolytic agents all act by converting
plasminogen to plasmin, which in turn cleaves
fibrinogen and fibrin leading to the formation
of fibrinogen/fibrin degradation products
(FDPs). three most commonly used
thrombolytic agents, streptokinase (SK),
urokinase (UK) and tissue plasminogen
activator (tPA ), tPA is the agent of choice at
doses ranging from 0.1-0.5 mg/kg/hour, with
the lower doses used when a catheter tip is
adjacent to the thrombus .

63. “Recommendations for neonatal treatment
are 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*”