Two things drive most UFH outcomes: the starting dose and how you read the first discordant lab. Reaching the therapeutic range early depends on an adequate initial weight-based dose, which may matter more than the exact target range (Anticoagulation Forum 2016). Any aPTT value in seconds, including the example on this card, is valid only for the reagent and analyzer it was calibrated on: use your lab’s heparin-calibrated range or an anti-Xa level. Adult dosing only. Confirm against your institutional nomogram before ordering.
Starting Nomogram by Indication
Indication
Bolus
Initial Infusion
Target
Notes
VTE treatment (DVT, PE)
80 units/kg
18 units/kg/h
Anti-Xa 0.3-0.7 IU/mL, or your lab’s calibrated aPTT range
Raschke 1993 RCT: 97% vs 77% reached the aPTT threshold within 24 h versus a fixed 5,000 unit + 1,000 units/h regimen; recurrent thromboembolism RR 5.0 with fixed dosing. Raschke used no bolus cap; many institutions add one.
ACS: NSTE-ACS, STEMI with fibrinolysis
60 units/kg, max 4,000 units
12 units/kg/h, max 1,000 units/h
aPTT 1.5-2.0× control (about 50-70 s), or protocol anti-Xa
ACC/AHA regimen (2014 NSTE-ACS; 2013 STEMI for the fibrinolysis aPTT target). The caps are part of the regimen and apply in obesity. The 2025 ACC/AHA ACS guideline keeps IV UFH as a Class 1 parenteral option in NSTE-ACS; confirm doses against its dosing table.
PCI (cath lab)
No GP IIb/IIIa: 70-100 units/kg. With GP IIb/IIIa: 50-70 units/kg.
Procedural; ACT-driven
ACT 250-300 s (HemoTec) or 300-350 s (Hemochron); 200-250 s with GP IIb/IIIa
2011 ACCF/AHA/SCAI PCI guideline (the ACC Bleeding Risk Toolkit lists 60-100 units/kg without GP IIb/IIIa). Reduce if already anticoagulated: give additional UFH to the ACT target. Fondaparinux must not be used to support PCI (2025 ACS, Class 3: Harm).
AF, LV thrombus, valve bridging, other “low-intensity”
Institutional
Institutional
Institutional
No guideline specifies a UFH nomogram for these. Many hospitals run them on the ACS-style 60/12 nomogram; others use the VTE nomogram. Know which one your order set picks.
No-bolus situations
No bolus
Typically 12-18 units/kg/h per protocol
Often a lower aPTT target (e.g., 50-70 s instead of 70-90 s)
Acute ischemic stroke when heparin is started for another indication, recent neurosurgery or intracranial hemorrhage risk, fresh post-procedure or post-op, high bleeding risk. Practice-based, not trial-based (no neurocritical care guideline addresses it).
Obtain total body weight, CBC (platelets), PT, and aPTT before starting (Anticoagulation Forum 2016). Urgent anticoagulation such as a heparin drip is not indicated for most patients with acute ischemic stroke (AHA/ASA 2019).
Dosing Weight in Obesity
Question
What the evidence says
Which weight?
Total (actual) body weight for weight-based UFH (Anticoagulation Forum 2016: total or adjusted weight can be used in obesity). A 2025 drug-information review of mostly small retrospective studies (no randomized trials) concluded the literature supports total body weight and that caps did not clearly shorten time to therapeutic range (UIC DIG 2025).
Should I cap?
ACS: yes (4,000 unit bolus, 1,000 units/h). VTE: institution-dependent. Empiric caps may increase the risk of initial under-anticoagulation (Anticoagulation Forum 2016). Published caps vary widely: one study comparing 4,000/1,000 caps with 10,000/2,250 caps found therapeutic aPTT at 6 h in 11% vs 23% (Floroff 2017).
Why watch closely anyway
Weight-normalized requirements fall as weight rises: about 16 units/kg/h under 100 kg versus 11.6 units/kg/h over 150 kg (George 2020). A total-weight start can overshoot later, so the first 6-hour level matters. Supporting studies did not include patients over 270 kg.
Monitoring
Test
Target
Notes
Anti-Xa (UFH-calibrated)
0.3-0.7 IU/mL for treatment
Same range regardless of instrument or reagent. Preferred with a prolonged baseline aPTT, suspected heparin resistance, or high fibrinogen or factor VIII. Cardiac and “low-intensity” protocols often use a lower range; those numbers are institutional, not guideline-defined.
aPTT
Your lab’s seconds range that corresponds to anti-Xa 0.3-0.7
The historical 1.5-2.5× control ratio is no longer recommended as a fixed target; its lower end often reflects subtherapeutic heparin. The range must be re-established with every reagent lot or instrument change. Heparin concentration explains less than half of aPTT variation.
Timing
6 h after start and after every change
Repeat q6h until two consecutive therapeutic results, then daily (Anticoagulation Forum 2016).
CBC
Baseline, then per HIT risk
Platelets and hemoglobin. Monitoring schedule in the HIT section below.
When anti-Xa and aPTT disagree
Pattern
Usual causes
What to do
aPTT low, anti-Xa therapeutic
High factor VIII and fibrinogen (acute phase: inflammation, post-op, pregnancy). Altered heparin responsiveness, not true resistance.
Do not raise the dose. If the anti-Xa is therapeutic, no adjustment is needed. Escalating on aPTT here risks over-anticoagulation.
Follow anti-Xa. A disproportionately prolonged aPTT relative to anti-Xa was associated with more major bleeding and death, so look for the cause.
Anti-Xa falsely high
Recent apixaban, rivaroxaban, or edoxaban; recent LMWH. The assay reads any anti-Xa activity.
Use aPTT until the oral Xa inhibitor or LMWH has cleared.
Anti-Xa falsely low
Marked hyperbilirubinemia, lipemia, hemolysis (interference thresholds are assay-specific).
Use aPTT; ask the lab for its interference limits.
Heparin resistance
Definition
Commonly >35,000 units/day without reaching target (Levine 1994). There is no consensus weight-based definition; a 2023 ISTH SSC communication proposing definitions drew a published rebuttal that favored validated weight-based nomograms over a single consensus definition.
Causes
Antithrombin deficiency, increased heparin clearance, increased heparin-binding proteins. High factor VIII or fibrinogen mimics resistance on aPTT only.
First step
Paired aPTT and anti-Xa. In Levine 1994 (patients needing ≥35,000 units/day), anti-Xa-guided dosing used less heparin with similar recurrent VTE (4.6% vs 6.1%) and bleeding (1.5% vs 6.1%, not significant).
Antithrombin
If the anti-Xa stays low on high doses, check antithrombin activity (and confirm the lab’s anti-Xa assay does not add exogenous antithrombin). Antithrombin replacement is not routine; more UFH or a direct thrombin inhibitor are alternatives.
Example titration table (Raschke-derived; EXAMPLE ONLY)
aPTT (s), ratio to control
Bolus
Infusion change
<35 (<1.2×)
80 units/kg
Increase by 4 units/kg/h
35-45 (1.2-1.5×)
40 units/kg
Increase by 2 units/kg/h
46-70 (1.5-2.3×)
None
No change
71-90 (2.3-3×)
None
Decrease by 2 units/kg/h
>90 (>3×)
None
Hold 1 h, then decrease by 3 units/kg/h
Recheck aPTT 6 h after each change. The 46-70 s band was meant to correspond to anti-Xa 0.3-0.7 on the original reagent. Your seconds will differ. Institutions also differ on bolus use for low results and on hold times. Use your own nomogram.
Platelet Monitoring and HIT
HIT risk (ASH 2018)
Examples
Platelet count monitoring
High (>1%)
UFH after major surgery or trauma (including cardiac surgery)
At least every other day
Intermediate (0.1-1%)
UFH in medical or obstetric patients; LMWH after major surgery or trauma
Every 2-3 days
Low (<0.1%)
LMWH in medical patients or after minor surgery; fondaparinux
Routine monitoring not recommended
Monitor from day 4 to day 14 or until heparin stops, whichever comes first. If heparin was given in the prior 30 days, start counts on day 0.
4Ts score (Lo 2006)
Domain
2 points
1 point
0 points
Thrombocytopenia
Fall >50% and nadir ≥20,000/µL
Fall 30-50%, or nadir 10,000-19,000/µL
Fall <30%, or nadir <10,000/µL
Timing
Clear onset day 5-10, or fall ≤1 day with heparin in the past 30 days
Consistent with day 5-10 but unclear; onset after day 10; or fall ≤1 day with heparin 30-100 days ago
Fall at <4 days without recent heparin
Thrombosis
New confirmed thrombosis, skin necrosis at heparin injection sites, or acute systemic reaction after IV UFH bolus
Progressive or recurrent thrombosis, non-necrotizing skin lesions, suspected unproven thrombosis
None
Other causes
None apparent
Possible
Definite
Score
Predictive value (Cuker 2012)
Action (ASH 2018)
0-3 Low
NPV 0.998
HIT unlikely. Do not send HIT testing; continue heparin if indicated. Recalculate if the picture changes. If key data are missing, score higher.
4-5 Intermediate
PPV 0.14
Stop heparin, start a non-heparin anticoagulant, send an immunoassay (PF4 ELISA or rapid test); confirm a positive with a functional assay (SRA). Prophylactic intensity only if bleeding risk is high and there is no other indication for therapeutic dosing.
6-8 High
PPV 0.64
Same, at therapeutic intensity. A functional assay is not required when the immunoassay is strongly positive (e.g., ELISA OD >2.0).
Acute HIT management (ASH 2018)
💡
Stop every heparin product, including flushes and lock solutions, and start a non-heparin anticoagulant whether or not thrombosis is present. LMWH is not an alternative.
💡
Image for silent DVT. In isolated HIT, bilateral lower-extremity compression ultrasound is suggested (silent DVT in 12-44% of asymptomatic patients), plus the arm with an upper-extremity central line.
💡
Duration. Isolated HIT: anticoagulate at least until platelets recover (usually ≥150 × 109/L), and generally not beyond 3 months. HIT with thrombosis: typically 3-6 months.
Non-heparin anticoagulants for HIT
Agent
Adult dose
Monitoring
Choose it when
Argatroban
2 mcg/kg/min, no bolus; max 10 mcg/kg/min (label). 0.5-1.2 mcg/kg/min for bilirubin >1.5 mg/dL, heart failure, anasarca, or post-cardiac surgery (ASH). Label: 0.5 mcg/kg/min in moderate-severe hepatic impairment.
aPTT 1.5-3× baseline, not over 100 s; check 2 h after start and each change. Get a baseline aPTT after heparin is stopped.
Critical illness, bleeding risk, possible procedure, renal failure. Avoid or reduce in Child-Pugh B/C.
Bivalirudin
0.15 mg/kg/h, no bolus (ASH). Example renal starting rates (UW Medicine): CrCl 30-60: 0.08; CrCl <30 or dialysis: 0.05 mg/kg/h.
aPTT 1.5-2.5× baseline (some centers use a dilute thrombin time)
Same settings as argatroban, and an option when hepatic dysfunction limits argatroban. Suggested agent for PCI in acute HIT. Off-label in HIT outside PCI.
Clinically stable patients. Contraindicated if CrCl <30 (label). Off-label for HIT.
Apixaban
HITT: 10 mg BID × 7 days, then 5 mg BID. Isolated HIT: 5 mg BID until platelet recovery.
None
Clinically stable, average bleeding risk. Not FDA-approved for HIT; doses extrapolated from VTE with limited evidence. Avoid in Child-Pugh B/C. Few patients with limb- or life-threatening thrombosis have been treated with DOACs.
Rivaroxaban
HITT: 15 mg BID × 3 weeks, then 20 mg daily. Isolated HIT: 15 mg BID until platelet recovery.
None
Dabigatran
HITT: 150 mg BID after ≥5 days of a parenteral non-heparin agent. Isolated HIT: 150 mg BID until platelet recovery.
None
💡
Transitions. A DOAC is suggested over warfarin and does not require waiting for platelet recovery: start it within 2 h of stopping argatroban or bivalirudin, or 24 h after the last fondaparinux dose (ASH pocket guide; the timing is general guidance, not a guideline recommendation). Renal replacement in acute HIT: argatroban or bivalirudin for circuit anticoagulation; citrate is not adequate when systemic anticoagulation is needed.
⚠️
Argatroban raises the INR on its own. When overlapping with warfarin: no warfarin loading dose; check INR daily. At argatroban ≤2 mcg/kg/min, stop argatroban when the combined INR is >4, recheck INR in 4-6 h, and restart argatroban if it falls below range (ASH uses <2). Repeat daily until warfarin alone is therapeutic. At doses above 2 mcg/kg/min, drop to 2 mcg/kg/min first and recheck INR in 4-6 h (label).
🛑 Danger Zone
☠️
Warfarin in acute HIT. Starting a VKA before platelet recovery is linked to venous limb gangrene, skin necrosis, and amputation (ASH: strong recommendation against). If the patient is already on warfarin at diagnosis, stop it and give IV vitamin K. Start warfarin only at platelets ≥150 × 109/L, overlap at least 5 days and until the INR is at target.
☠️
Chasing a low aPTT. In an inflamed ICU patient, escalating past 35,000 units/day on aPTT alone, without a paired anti-Xa, can produce a supratherapeutic heparin level hidden behind a “subtherapeutic” clotting time.
☠️
Borrowed seconds. Running another hospital’s aPTT nomogram (or the example above) on your reagent can place the whole range below or above true therapeutic heparin activity. Re-verify after every reagent lot change.
☠️
The wrong nomogram. A VTE bolus (80 units/kg, often uncapped) given to a stroke, fresh post-op, or post-fibrinolytic patient, or ACS dosing entered without its 4,000/1,000 caps. Check indication and caps on every heparin order.
☠️
Routine platelet transfusion in HIT. Suggested against at average bleeding risk; reserve it for active bleeding or high-risk procedures.