Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3865_Библиотеки_им_академика_М_И_Перельмана
.pdf
440 Anticoagulation Therapy
https://t.me/med1917
TABLE 18-18: Fondaparinux in HIT
Evidence
supporting
fondaparinux
Dosing Treatment of acute/recent thromboembolism: Dose may need to be
Monitoring antifactor Xa activity
Evidence
suggesting
caution
ACS: acute coronary syndrome, DVT: deep vein thrombosis, HIT: heparin-induced
thrombocytopenia, HITT: heparin-induced thrombocytopenia-related thrombosis syndrome,
sub-Q: subcutaneous
Note:
See Chapter 4 for details on fondaparinux and use outside HIT.
Several cohort studies with historical controls suggest that fondaparinux
is as effective as lepirudin or argatroban in the treatment of patients with
HIT or HITT. Case series studies have demonstrated that fondaparinux
may be a treatment option for suspected HIT, confirmed HIT, and postoperative cardiac or vascular surgery. A multi-center review revealed that
fondaparinux was used in 40% of suspected HIT cases.
modified in renal insufficiency.
• For patients who weigh <50 kg: 5 mg sub-Q daily
•
For patients who weigh 50–100 kg: 7.5 mg sub-Q daily
For patients who weigh >100 kg: 10 mg sub-Q daily
•
• Prophylaxis: (No need for full anticoagulation) 2.5 mg/day. In severe
renal impairment, 2.5 mg every other day has been used.
Fondaparinux 2.5 mg/day was effective if no indication for full
•
anticoagulation in one analysis.
The use of anti-factor Xa activity to monitor fondaparinux in HIT has not
been validated. Dose response was not observed in Phase II trials for DVT
or ACS.
Several cases suggesting fondaparinux as the cause of HIT have been
reported.
22-27
24
• It is unclear if the platelet count must be over
150 × 10
9
/L prior to starting warfarin. In the
presence of other causes of thrombocytopenia
or patients with low baseline platelet counts,
alternative anticoagulant therapy can go for very
long periods of time and be very costly.
Options once platelet count has begun
recovery and the patient can tolerate longer
acting anticoagulants: Fondaparinux or
starting warfarin at conservative doses can be
considered.
HEPARIN-INDUCED THROMBOCYTOPENIA 441
https://t.me/med1917
TABLE 18-19: Use of Warfarin in HIT
Initial recognition of
HIT (acute HIT)
Place in therapy A majority of patients in the lepirudin and argatroban trials were
Monitoring INR, targeting a value of 2–3 if not an a DTI causing false INR elevation
Transitioning from a
DTI to warfarin when
a DTI is present
Use of warfarin is not recommended, and if present at the time of HIT
recognition, it should be reversed (ACCP grade 2C); monotherapy with
warfarin as the initial means to manage HIT is not recommended; if
possible, 5 days of overlapping therapy with a DTI until platelet count
has recovered and the INR is >2 (or higher if on some DTI therapies);
evidence supporting this is weak. ACCP defines platelet recovery
as 150 x 10
effective to initiate warfarin after two consecutive platelet count
increases regardless of the absolute platelet count.
converted to warfarin for extended anticoagulation; duration for
isolated HIT has been until stable recovery of platelets and reduced
risk for thrombosis; in some settings, clinicians may complete 30 days
of alternative anticoagulation; longer therapy may be considered in
the presence of thrombosis or when other indications for continued
anticoagulation are present; based on case reports, initial dosing should
be conservative to decrease the risk for venous limb gangrene.
(see Chapter 5); in the setting of false INR elevations with concurrent
DTI therapy; chromogenic factor X levels of 11–42% (similar to an INR
of 2–3.5) can be used (see Chapter 5).
It is important to note that the assay for the INR and aPTT separately
may be unique to each institution; further, other variables could
be affecting the INR at a given DTI dose; these reasons can make
the standard nomogram for argatroban provided in the prescribing
information packet difficult to use.
One alternative approach is the following:
1.
2.
3.
9
/L, but a single center study suggests that it is safe and
Draw a baseline INR with an aPTT on DTI therapy alone.
Initiate warfarin and identify a desired 1.5–2 point increase in the
INR or a preselected INR, which considers the DTI-induced INR
prolongation (with minimal change in the aPTT).
Once the desired number of overlap days and desired platelet
recovery has occurred and the desired INR target is reached, hold
the DTI for 4–8 hr and recheck the INR and aPTT; if the INR is
between 2–3 with an aPTT value close to baseline (INR is being
elevated by warfarin alone since aPTT close to baseline), then the
DTI can be discontinued; it may take longer for the effects of a DTI
to diminish if a very low infusion rate with aPTT values in the target
range.
4,5,12,28-30
ACCP: American College of CHEST Physicians, aPTT: activated partial thromboplastin time, DTI:
direct thrombin inhibitor, HIT: heparin-induced thrombocytopenia, INR: international normalized
ratio
442 Anticoagulation Therapy
https://t.me/med1917
Recommendations on When to Begin Therapy
See Figure 18-1 for recommendations on when to begin therapy for HIT.
American College of Chest Physicians’ recommendation regarding patients
with a confirmed history of HIT to avoid a recurrence of HIT5:
•
To avoid re-exposure to heparin and LMWH, in patients with history of HIT or
heparin allergy needing venous thromboembolism prophylaxis:
Consider warfarin, danaparoid, fondaparinux, apixaban, dabigatran,
and rivaroxaban for pharmacologic prophylaxis.
Consider nonpharmacologic deep venous thromboembolism
prophylaxis.
May consider cautiously using a heparin product if:
Unable to avoid UFH or LMWH options
More than 100 days since HIT diagnosis
Duration of heparin therapy is limited
•
Patients with history of HIT and acute thrombosis not related to HIT:
Use fondaparinux at therapeutic doses until transition to warfarin
can be achieved (Grade 2C)
Do not use warfarin alone
•
Patients with history of HIT requiring ongoing renal replacement therapy (RRT):
Use regional citrate (Grade 2C)
SPECIAL POPULATION
CONSIDERATIONS
5,12,31-35
Acute Coronary Syndromes
•
Alternative anticoagulant considerations
Antiplatelet inhibitor or direct thrombin inhibitor or combination.
Enoxaparin is preferred over heparin for anticoagulation >48 hours
to minimize the risk of developing HIT.
Ability of glycoprotein IIb-IIIa inhibitors to block platelet response
in HIT during PCI or acute HIT is unknown.
•
Percutaneous coronary intervention (PCI) dosing under HIT conditions
Fondaparinux should not be given as the sole anticoagulant and
is contraindicated in CrCl <30 mL/min.
Bivalirudin (Grade 2B) or argatroban (Grade 2C) are preferred over
other treatment options.
The dosing regimen used may depend on the ACS
setting and a history of HIT versus active HIT. During
PCI, a higher dose per the prescribing indication may
be used. In selected situations, a lower dose (e.g.,
0.2 mg/kg/hr) may be done for a short period of time
immediately after catheterization. Otherwise, the typical
HEPARIN-INDUCED THROMBOCYTOPENIA 443
https://t.me/med1917
regimen for HIT management if an alternate anticoagulant is necessary can be considered.
Cardiac Surgery
•
History of HIT
Antibody negative: Use of UFH intraoperatively is preferred (Grade
5,31,35,36
2C).
Antibody positive: Check washed platelet aggregation assay, if
negative, use UFH intraoperatively; if positive, use nonheparin
anticoagulants (Grade 2C).
Consider using a nonheparin agent postoperatively if possible.
In one case series (n=11), plasmapheresis using fresh frozen plasma for
replacement with heparin re-exposure during cardiopulmonary bypass was
used successfully.31 Separately, eponesesterol or tirofiban concurrent with
heparin have been used during surgery.
•
Acute or subacute HIT
If possible, delay surgery until HIT resolved and antibody negative
or weak positive (Grade 2C).
Antibody positive: Bivalirudin is preferred over other treatment
options (Grade 2C).
If heparin antibodies are absent, heparin use intraoperatively is
preferred (Grade 2C); avoid perioperative heparin use.
UFH infusion combined with a parenteral antiplatelet agent infusion
(e.g., tirofiban) (Grade 2C—see Table 18-21).
Danaparoid (off-pump procedures) (Grade 2C).
Pregnancy, Pediatrics, and Other (i.e., ECLS, Impella
Devices)
•
Pregnancy
HIT in this population is rare.
Special considerations: HIT antibodies cross the placenta.
Pregnancy-induced increases in cardiac output, renal clearance,
Danaparoid is preferred (Grade 2C); fondaparinux can be used if
• If bivalirudin is used intraoperatively,
ultrafiltration can be performed via the
cardiopulmonary bypass circuit prior to chest
closure to remove bivalirudin and decrease
perioperative bleeding.
blood volume, and weight may require doses different to that of
the general population.
danaparoid is not available (Grade 2C).
444 Anticoagulation Therapy
https://t.me/med1917
Fondaparinux/danaparoid have the most supportive data for this
population and condition.
Special consideration: fondaparinux crosses the placenta.
Long-term anticoagulation: subcutaneous danaparoid, lepirudin,
or fondaparinux.
Target: not established, but consider monitoring aPTT (parenteral
DTI); anti-factor Xa (danaparoid).
•
Pediatrics (Table 18-20)
Pathophysiology and frequency similar to that of adult population.
Most pediatric cases reported in critically ill or cardiac surgery
patients.
Use of LMWH may decrease likelihood of HIT.
Body weight may be correlated with DTI clearance.
•
For patients with HIT on extracorporeal life support (ECLS, ECMO): See Chapter
5 on dosing.
•
For patients with HIT with Impella Devices: It is not clear how an alternate anticoagulant should be used and if that includes systemic anticoagulation, or additional
to the purge solution.
TABLE 18-20: Suggested Alternative Anticoagulant Dosing in
Pediatric Patients Under HIT Conditions (See Table 5-10)
Agent Dose Comments
Argatroban In normal hepatic function, doses
similar to observations in adults may
apply; younger patients <6 months
old may have lower clearance and
require a lower dose.
Bivalirudin Infusion of 0.05–0.31 mg/kg/hour
If deemed necessary in selected
settings (e.g., ECLS), a bolus dose
0.1–0.25 mg/kg has been used.
Danaparoid VTE prevention:
10 units/kg sub-Q BID
VTE treatment:
Bolus: 30 units/kg IV
Infusion: 1.2–2 units/kg/hr
BID: twice daily, ECLS: extracorporeal life support, HIT: heparin-induced thrombocytopenia, IV:
intravenous, sub-Q: subcutaneous, VTE: venous thromboembolism, yr: year
Higher doses may be necessary in the
setting of ECLS.
The higher doses may occur in ECLS.
Can be removed by hemofiltration.
Elimination may be blunted in
hypothermia.
Renal dialysis:
<10 yr: 30 units/kg IV + 1,000 units
before each of first two dialysis sessions
≥10–17 yr: 30 units/kg IV + 1,500 units
before each of first two dialysis sessions
Anti-factor Xa target on day 3:
0.4–0.6 units/mL (0.5–0.8 units/mL for
high dose)
34
Maintaining Lines in HIT Patients
See Table 18-21.
HEPARIN-INDUCED THROMBOCYTOPENIA 445
https://t.me/med1917
TABLE 18-21: Considerations for Maintaining Lines in the
Setting of HIT
Agent Comments
0.9% saline None
Citrate 4% has been studied; volume depends on the line; flush drawn from
Bivalirudin Not recommended as a flush because of enzymatic degradation by
HIT: heparin-induced thrombocytopenia
the Abbott ACD-A solution has been used
thrombin
See Table 18-22.
TABLE 18-22: Dosing of Alternative Agents in Bypass Graft
Surgery Procedures
Agent Dosing
DTI See Chapter 5 for DTI dosing insights.
Tirofiban Of the parenteral GP IIb/IIIa inhibitors, tirofiban has a shorter duration of
Epoprostenol Prior to starting heparin, initiate infusion at 5 ng/kg/min, increasing as
35-37
effect and complete binding to the PG IIB/IIIa receptor
Regimen: Stop DTI if being infused prior to cannulation; initiate tirofiban
(bolus 10 mcg/kg followed by a continuous infusion of 0.15 mcg/kg/
min) 10 min prior to cannulation for cardiopulmonary bypass and prior
to starting heparin; initiate UFH at 400 units/kg targeting an ACT of 480
sec; bolus UFH as necessary to maintain ACT of 480 sec; stop tirofiban
infusion 1 hr before conclusion of cardiopulmonary bypass; reverse
UFH with protamine as necessary; begin thromboprophylaxis with DTI
targeting a aPTT of 40–60 sec or 1.5–2.5 x control.
tolerated until target of 30 ng/kg/min is reached; standard heparin during
surgery; norepinephrine may need to be used to manage hypotension;
delay heparinization as long as possible (just prior to aortic canalization).
36
Plasmapheresis One case series studied the use of plasmapheresis for HIT management
Immunomodulation One case series suggested that IVIG, with plasmapheresis if needed,
ACT: activated clotting time, aPTT: activated partial thromboplastin time, DTI: direct thrombin
inhibitor, GP: glycoprotein, HIT: heparin-induced thrombocytopenia, IVIG: intravenous
immunoglobulin, sec: seconds, UFH: unfractionated heparin, x: times
in cardiac surgery patients with history of HIT and positive heparin
antibodies at the time of surgery. Plasmapheresis decreased heparin
antibody titers by 50–85%, and all complications were deemed to be
unrelated to HIT.
could be given to patients with general immune dysfunction who
developed profound thrombocytopenia after cardiac surgery. Platelet
counts started recovering within 5 days of IVIG administration and 95% of
patients recovered to survive hospitalization.
446 Anticoagulation Therapy
https://t.me/med1917
REFERENCES AND KEY ARTICLES*
1. Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N
Engl J Med. 2001;344(17):1286-1292.
*2. Warkentin TE. Heparin-induced thrombocytopenia: pathogenesis and management. Br
J Haematol. 2003;121(4):535-555.
*3. Cuker A. Management of the multiple phases of heparin-induced thrombocytopenia.
Thromb Haemost. 2016;116:835-842.
*4. Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia. 4th ed. New
York, NY: Informa Healthcare USA, Inc; 2008.
*5. Linkins LA, Dans AL, Moores LK et al. Treatment and prevention of heparin-induced
thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis. 9th ed.
Chest. 2012;141:e495s-e530s.
*6.
Greinacher A, Warkentin TE. Recognition, treatment, and prevention of heparin-
induced thrombocytopenia: review and update. Thromb Res. 2006;118:165-176.
7. Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N Engl J
Med. 2006;355:809-817.
8. Chong BH, Chong JH. Heparin-induced thrombocytopenia. Expert Rev Cardiovasc
Ther. 2004;2:547-559.
9. Lillo-Le Louet A, Boutouyrie P, Alhenc-Gelas M, et al. Diagnostic score for heparininduced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost.
2004;2:1882-1888.
Warkentin TE. Laboratory testing for heparin-induced thrombocytopenia. J Thromb
10.
Thrombolysis. 2001;10(Suppl 1):35-45.
*11. Warkentin TE. New approaches to the diagnosis of heparin-induced thrombocytopenia.
Chest. 2005;127(2 Suppl):35S-45S.
*12. Dager WE, Dougherty JA, Nguyen PH, et al. Heparin-induced thrombocytopenia:
a review of treatment options and special considerations. Pharmacotherapy.
2007;27:564-587.
13.
Huhle G, Hoffmann U, Hoffmann I, et al. A new therapeutic option by subcutaneous
recombinant hirudin in patients with heparin-induced thrombocytopenia type II: a
pilot study. Thromb Res. 2000;99:325-334.
14. Miyares MA, Davis KA. Direct-acting oral anticoagulants as emerging treatment options
for heparin-induced thrombocytopenia. Ann Pharmacotherapy. 2015;49:735-739.
15. Hourmouzis Z, Bhalla MC, Frey JA, et al. Pulmonary embolism and heparininduced thrombocytopenia successfully treated with tissue plasminogen activator and
argatroban. Am J Emerg Med. 2015;33:739.e5-6.
16. Lewis BE, Wallis DE, Berkowitz SD, et al. Argatroban anticoagulant therapy in patients
with heparin-induced thrombocytopenia. Circulation. 2001;103:1838-1843.
17. Lewis BE, Wallis DE, Leya F, et al. Argatroban anticoagulation in patients with
heparin-induced thrombocytopenia. Arch Intern Med. 2003;163:1849-1856.
18. Francis JL, Drexler A, Gwyn G, et al. Successful use of bivalirudin in the treatment
of patients suspected or at risk of, heparin-induced thrombocytopenia. Blood.
2004;104:Abstract 4077.
HEPARIN-INDUCED THROMBOCYTOPENIA 447
https://t.me/med1917
19. Joseph L, Casanegra AI, Dhariwal M, et al. Bivalirudin for the treatment of patients
with confirmed or suspected heparin-induced thrombocytopenia. J Thromb Haemost.
2014;12:1044-1053.
Tsu LV, Dager WE. Bivalirudin dosing adjustments for reduced renal function with or
20.
without hemodialysis in the management of heparin-induced thrombocytopenia. Ann
Pharmacother. 2011;45:1185-1192.
Magnani HN, Gallus A. Heparin-induced thrombocytopenia (HIT). A report of 1478
21.
clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-
2004. Thromb Haemost. 2006;95:967-981.
22.
Grouzi E, Kyriakou E, Panagou I, et al. Fondaparinux for the treatment of acute
heparin-induced thrombocytopenia: a single center experience. Clin Appl Thromb
Hemost. 2009 Oct 13. [Epub ahead of print]
Lobo B, Finch C, Howard A. Fondaparinux for the treatment of patients with acute
23.
heparin-induced thrombocytopenia. Thromb Haemost. 2008;99:208-214.
24. Kang M, Alahmadi M, Sawh S, et al. Fondaparinux for the treatment of suspected
heparin-induced thrombocytopenia: a propensity score-matched study. Blood.
2015;125:924-929.
25.
Warkentin TE, Pai M, Sheppard JI, et al. Fondaparinux treatment of acute heparin-
induced thrombocytopenia confirmed by the serotonin-release assay: a 30 month,
16-patient case series. J Thromb Haemost. 2011;9:2389-2396.
Schindewolf M, Steindl J, Beyer-Westendorf J, et al. Frequent off-label use of
26.
fondaparinux in patients with suspected acute heparin-induced thrombocytopenia
(HIT)—findings from the GerHIT multi-centre registry study. Thromb Res.
2014;134:29-35.
27. Burch M, Cooper B. Fondaparinux-associated heparin-induced thrombocytopenia. Proc
(Bayl Univ Med Cent). 2012;25:13-15.
28. Arpino PA, Demirjian Z, Van Cott EM. Use of the chromogenic factor X assay to predict
the international normalized ratio in patients transitioning from argatroban to warfarin.
Pharmacotherapy. 2005;25:157-164.
29. Gosselin RC, Dager WE, King JH, et al. Effect of direct thrombin-inhibitors:
bivalirudin, lepirudin and argatroban, on prothrombin time and INR measurements.
Am J Clin Path. 2004;121:593-599.
30.
Chen L, Dager WE, Roberts AJ. Safety and efficacy of starting warfarin after two
consecutive platelet rises in patients with heparin-induced thrombocytopenia
[abstract]. Abstracts of the XXI Congress of the International Society of Thrombosis and
Haemostasis 2015. J Thromb Haemost. 2015;13:S2-866. Abstract #PO312-WED.
Welsby IJ, Um J, Milano CA, et al. Plasmapheresis and heparin reexposure as
31.
a management strategy for cardiac surgical patients with heparin-induced
thrombocytopenia. Anesth Analg. 2010;110:30-35.
32. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the
management of patients with non-ST-elevation acute coronary syndromes. Circulation.
2014;130:e344-e426.
33. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for
the management of ST-elevation myocardial infarction. J Am Coll Cardiol.
2013;61:e78-e140.
448 Anticoagulation Therapy
https://t.me/med1917
34. Risch L, Fisher JE, Herklotz R, et al. Heparin-induced thrombocytopenia in
paediatrics: clinical characteristics, therapy and outcomes. Intensive Care Med.
2004;30:1615-1624.
Greinacher A. The use of direct thrombin inhibitors in cardiovascular surgery in patients
35.
with heparin-induced thrombocytopenia. Semin Thromb Hemost. 2004;30:315-327.
36. Koster A, Meyer O, Fisher T, et al. One-year experience with the platelet glycoprotein
IIb/IIIa antagonist tirofiban and heparin during cardiopulmonary bypass in patients
with heparin-induced thrombocytopenia type II. J Thorac Cardiovasc Surg.
2001;122:1254-1255.
37. Rankin JS, Stratton CW. Efficacy of immunomodulation in the treatment of
profound thrombocytopenia after adult cardiac surgery. J Thorac Cardiovasc Surg.
2014;147;808-815.
19
https://t.me/med1917
Chapter
PREGNANCY
Nancy L. Shapiro
INTRODUCTION
Pregnancy is considered an acquired hypercoagulable state due to increased
concentrations of several clotting factors, increased fibrinogen, and reductions in
the natural anticoagulants free protein S and antithrombin.
coagulability during pregnancy predisposes the mother to deep vein thrombosis
(DVT) and pulmonary embolism (PE), and the fetus to gestational complications
of recurrent pregnancy loss, intrauterine growth restriction, preeclampsia, and
placental abruption. These complications affect up to 15% of pregnancies, and
they are a major cause of fetal morbidity and mortality.3 The risk of venous thromboembolism (VTE), composed of DVT and PE, is 2- to 5-fold higher in pregnancy
compared to nonpregnant women of child-bearing age.
VTE ranges between 0.5 to 2 women per 1,000 pregnancies. Most symptomatic
cases are DVT, with two-thirds of cases occurring antepartum, and half of these
events occurring before the third trimester.
in pregnant women but occurs more often in the postpartum period than during
pregnancy. In the postpartum period, the risk of VTE has been estimated to be
increased 20-fold. VTE accounts for 1.1 deaths per 100,000 deliveries or 10% of
all maternal deaths.
in pregnant patients with mechanical heart valves, selection of a safe anticoagulant, management of a patient on a direct-acting oral anticoagulant (DOAC) who
becomes pregnant, and peripartum anticoagulation management.
9
Areas of controversy include management of anticoagulation
7,8
PE is the leading cause of mortality
1,2
The increase in hyper-
1,2,4-6
The incidence of
USE OF ANTICOAGULANTS DURING
PREGNANCY AND LACTATION
Anticoagulation is used in pregnancy for the prevention and treatment of thrombosis, as well as for the prevention of pregnancy loss. A summary of indications
for anticoagulation use in pregnancy can be found in Table 19-1. The definitions
used by the American College of Chest Physicians (ACCP), the American College of
Obstetrics and Gynecology (ACOG), and the American Heart Association (AHA) for
their grades of recommendations are provided in Table 19-2 and will be referred
to throughout the chapter.
449
Соседние файлы в папке Библиотека им академика М.И. Перельмана