Circulating blood volumes for adults and peds are shown in Table 9.1.
Definition: replacement of > 1 blood volume (in average adult ≈ 20 U) in < 24 hrs for adult, or > 2 × circulating blood volume in peds, may cause dilution of effective platelets and coagulation factors. When operating on a pediatric patient, you can usually safely replace up to 1.5 × the circulating blood volume before problems with coagulopathy ensue.
Major histocompatibilities of blood are shown in Table 9.2.
For peds, use Eq Equation 9.1.
Patients may donate every 3 days to 1 week as long as they maintain Hct ≥ 34% (supplement with ferrous sulfate). The following patients require physician release before donating: patients with coronary artery disease, angina, cerebrovascular disease, seizure disorder, pregnancy (because of possible vasovagal episode) or patients with malignancy.
Normal platelet count (PC) is 150K-400K (abbreviation used here: 150K = 150,000/mm3 = 150×109/l). Thrombocytopenia is defined as PC < 150K. Bleeding (spontaneously or with invasive procedures) is rarely a problem with PC > 50K. Spontaneous hemorrhage is very likely with PC < 5K. Spontaneous intracranial hemorrhage is uncommon with PC > 30K, and is more common in adults than children. Based on patients with ITP, the risk of fatal hemorrhage in patients with PC < 30K is 0.0162–0.0389 cases per patient-year1 (risk of death from infection is higher). Intracranial bleeding is usually subarachnoid or intraparenchymal, with petechial hemorrhages common.
Indications for platelet transfusion2 :
platelet transfusions have limited usefulness when thrombocytopenia is due to platelet destruction (e.g. by antibodies as in ITTP) or consumption (if production is adequate or increased, platelet transfusion usually will not be useful)
documented platelet dysfunction in a patient scheduled for surgery or in a patient with advanced hepatic and/or renal insufficiency (consider pharmacologic enhancement of platelet function, e.g. desmopressin3 )
Adult: 1 U raises platelet count by ≈ 5–10K. Typical dose for thrombocytopenic bleeding adult: 6–10 U (usual order: “8-pack”). Alternatively, 1 U of pheresed platelets may be given (obtained from a single donor by apheresis, equivalent to 8–10 U of pooled donor platelets).
Check PC 1–2 hrs after transfusion. The increase in PC will be less in DIC, sepsis, splenomegaly, with platelet antibodies, or if the patient is on chemotherapy. In the absence of increased consumption, platelets will be needed q 3–5 days.
1 bag = 200–250 ml (usually referred to as a “unit”, not to be confused with 1 unit of factor activity which is defined as 1 ml). FFP is plasma separated from RBCs and platelets, and contains all coagulation factors and natural inhibitors. FFP has an out-date period of 12 months. The risk of AIDS and hepatitis for each unit of FFP is equal to that of a whole unit of blood.
Recommendations (modified2 ):
history or clinical course suggestive of coagulopathy due to congenital or acquired coagulation factor deficiency with active bleeding or pre-op, with PT > 18 sec or APTT > 1.5 × upper limit of normal (usually > 55 sec), fibrinogen functioning normally and level > 1 g/l, and coagulation factor assay < 25% activity
reversal of warfarin (Coumadin®) effect (PT > 18 sec, or INR > 1.6) in patient actively bleeding or requiring emergency surgery or procedure with insufficient time for vitamin K to correct (which usually requires > 6–12 hrs)
Usual starting dose is 2 bags of FFP (400–600 ml). If PT is 18–22 secs or APTT is 55–70 secs, 1 bag may suffice. Doses as high as 10–15 ml/kg may be needed for some patients. Monitor PT/PTT (or specific factor assay) and clinical bleeding. Since factor VII has a shorter half-life (≈ 6 hrs) than the other factors, PT may become prolonged before APTT.
Usually from outdated blood, treated to inactivate hepatitis B virus. Ratio of albumin:globulin percentage in “albumin” is 96%:4%, in PPF it is 83%:17%. Available in 5% (oncotically and osmotically equivalent to plasma) and 25% (contraindicated in dehydrated patients). 25% albumin may be diluted to 5% by mixing 1 volume of 25% albumin to 4 volumes of D5W or 0.9% NS (✖ caution: mixing with sterile water will result in a hypotonic solution that can cause hemolysis and possible renal failure).
Expensive for use simply as a volume expander (≈ $60–80 per unit). Indicated only when total protein < 5.2 gm% (otherwise, use crystalloid which is equally effective). Rapid infusion (> 10 cc/min) has been reported to cause hypotension (due to Na-acetate and Hageman factor fragments). Use in ARDS is controversial. In neurosurgical patients, may be considered as an adjunct for volume expansion (along with crystalloids) for hyperdynamic therapy when the hematocrit is < 40% following SAH where there is concern about increasing the risk of rebleeding e.g. with the use of hetastarch.
Derived from fresh-frozen human plasma, contains clotting factors II, VII, IX and X, with protein C & S to prevent thrombosis. Primary indication is to be given IV to reverse warfarin in emergency situations. However it is also used in other settings. Requires much lower volume than FFP to work. Also, when the INR gets down to about 1.4, PCC will continue to reduce the INR whereas FFP will have little or no benefit.
Optimal dosing is not known. Doses of 15-50 IU/kg have been given to hemophiliacs, but the clotting deficit differs in vitamin-K depletion than in clotting factor absence. A reasonable dose that is often used is 25 IU/kg.
Most of these issues have not been studied in a rigorous, prospective fashion. Yet, these questions frequently arise. The following is to be considered a framework of guidelines, and is not to be construed as a standard of care. Table 9.3 acts as an index to the topics discussed below.
Starting/continuing anticoagulation in the presence of the following neurosurgical conditions
Managing patients who are already anticoagulated who need a neurosurgical procedure
Contraindications to heparin therapy are constantly being reevaluated. Massive PE producing hemodynamic compromise should be treated with anticoagulation in most cases despite intracranial risks. Contraindications to full anticoagulation with heparin include:
Anticoagulation may not increase the risk of hemorrhage (i.e. rupture), however, should rupture occur, anticoagulation would most likely increase volume of hemorrhage and thus increase morbidity and mortality.
The decision to start/continue anticoagulant depends on the indication for the drugs, the size of the aneurysm (a small aneurysm < 4 mm is not as worrisome). Patients needing Plavix® for drug-eluting cardiac stents should probably be left on their drugs.
Some authors are reluctant to administer full-dose heparin to a patient with a brain tumor,4 although a number of studies found no higher risk in these patients when treated with heparin or oral anticoagulation5 , 6 , 7 (PT should be followed very closely, one study recommended maintaining PT ≈ 1.25 × control7 ).
Requires individualization based on the reason for the craniotomy. Surgery for parenchymal lesions where the surgery disrupts small vessels (e.g. brain tumor) is probably higher risk for hemorrhage than e.g. aneurysm surgery (expert opinion). Options:
Full anticoagulation: most neurosurgeons would probably not fully anticoagulate patients < 3–5 days following craniotomy,8 and some recommend at least 2 weeks. However, one study found no increased incidence of bleeding when anticoagulation was resumed 3 days post craniotomy.9
Low-dose (prophylactic) anticoagulation: either with mini-dose heparin (5000 U SQ 2 hrs prior to craniotomy and continuing q 12 hrs post-op × 7 d) or enoxaparin (Lovenox) (30 mg SQ BID or as a single dose of 40 MG SQ q d). – RPDB study10 : assessed safety (not efficacy), 55 patients undergoing craniotomy for tumor received mini-dose heparin as indicated had no increased bleeding tendency by any of the parameters measured. RPNB study11 : incidence of post-op hemorrhage increased to 11% with enoxaparin.
Pre-operative laboratory assessment of the coagulation pathway and platelet function is routinely used even though these studies rarely contribute critical information in the patient with a negative history for bleeding tendencies. There are no randomized studies to assess the value of coagulation laboratory measurements to patient care. This section encompasses the use of antiplatelet and anticoagulation medicines, their monitoring, and their reversal.
Table 9.4 summarizes this information.
Patients on warfarin who must be anticoagulated as long as possible (e.g. mechanical heart valves) may be “bridged“ to LMW heparin injections, e.g. Lovenox, as follows: stop warfarin at least 3 days prior to the procedure, and begin self-administered LMW heparin injections which are discontinued as outlined in Table 9.4.
Patients with less critical anticoagulation needs (e.g. chronic a-fib) can usually stop the warfarin at least 4–5 days before the procedure, and a PT/INR is then checked on admission to the hospital. Patients must be advised that during the time that they are not anticoagulated, they are at risk of possible complications from the condition for which they are receiving the agents (annual risk for mechanical valve: ≈ 6%; for a-fib: depends on several factors including age & history of prior stroke, an average for patients > 65 years age is ≈ 5–6%; see details.
For procedures where post-op mass effect from bleeding would pose serious risk (which includes most neurosurgical operations), it is recommended that the PT should be ≈ ≤ 13.5 sec (i.e. ≤ upper limits of normal) or the INR should be ≈ ≤ 1.4 (e.g. for reference, this INR is considered safe for performing a percutaneous needle liver biopsy). See also reversal of anticoagulation.
Give FFP (start with 2 units) and vitamin K (10–20 mg IV at ≤ 1 mg/min) as soon as possible; see also reversal of anticoagulation. The timing of surgery is then based on the urgency of the situation and the nature of the procedure (e.g. the decision might be to evacuate a spinal epidural hematoma in an acutely paralyzed patient before anticoagulation is fully reversed).
For emergencies: if it would be deleterious to wait 4–6 hours after discontinuing heparin and then repeating the PTT to verify that anticoagulation has been corrected, then heparin can be reversed with protamine.
For emergencies: can be reversed with protamine.
Non-emergencies: See Table 9.4. Longer times are needed in renal failure. A factor Xa level can be used to check anticoagulation status, but this usually must be sent out, making it unsuitable for acute management.
Platelets are important for maintaining vascular endothelial integrity and are constantly involved with hemostasis in conjunction with coagulation factors. Severe thrombocytopenia can result in petechial hemorrhages or spontaneous intracerebral hemorrhage (ICH). Vascular wall disturbance is the initial stimulus for platelet deposition and activation. Platelets adhere to collagen via surface receptors GPIb-V-IX and von Willebrand factor. This adhesion sets off a cascade of reactions, which result in platelet aggregation forming a hemostatic plug. Historically, bleeding time (BT) was used as the screening test for abnormalities of platelet function. Due to unreliability, many institutions have replaced the BT with the platelet function assay (PFA) using the PFA-100 (platelet function analyzer). There are limited studies confirming its use according to the International Society of Thrombosis and Hemostasis.12 , 13
In the PFA-100, primary hemostasis is simulated under “high-shear” flow by movement of citrated blood through a membrane-impregnated capillary in two collagen-coated cartridges; one stimulates platelets with adenosine diphosphate (ADP) and the other with epinephrine.14 This interaction with the collagen induces a platelet plug, which closes an aperture. Results are reported as closure time in seconds. This method is eligible as a screening test for primary hemostatic disease such as von Willebrand disease as well as for monitoring the effect of antiplatelet therapy. The PFA-100 works for testing with aspirin but not with thienopyridine drug class (e.g. clopidogrel). Newly available PFA cartridges detect P2Y12 receptor blockade in patients on theinopyridine drugs.15 VerifyNow® measures agonist-induced aggregation as an increase in light transmittance. The system contains a preparation of human fibrinogen-coated beads, which cause a change in light transmittance by ADP-induced platelet aggregation.15 There is little correlation between PFA-100 results and VerifyNow Assay.
Plavix® (clopidogrel)and aspirin
Cause permanent inhibition of platelet function that persists ≈ 5 days after discontinuation of the drug and can increase the risk of bleeding. For elective cases, 5–7 days off these drugs is recommended (surveys of German neurosurgeons16 , 17 : an average of 7 days was used for low-dose ASA, with a few who do spine surgery even while the patient is on ASA).
Cardiac stents: dual antiplatelet therapy (e.g. ASA + Plavix®) are mandatory for 4 weeks (90 days is preferable18 ) after placement of a bare metal cardiac stent, and for at least 1 year with drug-eluting stents (DES) (the risk declines from ≈ 6% to ≈ 3%).19 Even short gaps in drug therapy (e.g. to perform neurosurgical procedures) is associated with significant risk of acute stent occlusion (and therefore elective surgery during this time is discouraged20 ). DES are so effective in suppressing endothelialization that lifetime dual antiplatelet therapy may be required. Bridging DES patients with antithrombin, anticoagulants, or glycoprotein IIb/IIIa agents has not been proven effective.20
Reversal of antiplatelet drugs: While heparin and warfarin can be reliably and measurably reversed, the situation is less clear with antiplatelet agents.21 Agents used pre-op to reverse these drugs include: Desmopressin (DDAVP®)16 , 17 and FFP.16
Reversal of Plavix for emergency surgery: platelets may be given, however, Plavix effects persists for up to a couple of days after the last dose, and can actually inhibit platelets given after the drug is discontinued (the half-life of aspirin is lower and should not be an issue after 1 day). In cases with continued oozing in the first day or so after discontinuing Plavix, the following regimen is an option:
recombinant activated coagulation factor VII (rFVIIa): even though the defect is in the platelets, rFVIIa works, via a mechanism not mediated by protein clotting factors. Very expensive (≈ $10,000 per dose), but this must be balanced against the cost of repeat craniotomy, increased ICU stay and additional morbidity
initial dose22 : 90–120 mcg/kg
Herbal products and supplements
Herbal products and supplements often affect platelet aggregation and the coagulation cascade by means that cannot be detected by laboratory tests. The increasing popularity of these unregulated products requires screening patients for their use. There are limited studies regarding the use of herbal supplements in neurosurgery and for an elective operation waiting 7–14 days after cessation of their use is warranted.
Fish Oil (Omega-3 Fatty Acids) is widely used among the cardiac and general population for treatment of dyslipidemia and hypertriglyceridemia. Fish oil may affect platelet aggregation by a reduction in arachnadonic acid and thomboxane and adenosine diphosphate receptor blockade. Fish oil may also potentially lengthen bleeding times.23 , 24 , 25
Garlic (Allium sativum) has increased in popularity as a supplement. Purported benefits include: lowering blood pressure, preventing infection and myocardial infarction, and treating hypercholesterolemia. Garlic has an antiplatelet affect through ADP receptor blockade, and reducing calcium and thromboxane.26 There is particular concern with garlic as it may potentiate the antiplatelet or anticoagulant affect of aspirin or warfarin.27
Ginkgo (Ginkgo biloba) has also become a popular supplement found in many formulations from capsules to energy drinks. Ginkgo has been used to treat a number of ailments including memory loss, depression, anxiety, dizziness, claudication, erectile dysfunction, tinnitus and headache. Ginkgo affects bleeding via an antiplatelet effect and antagonism of platelet-activating factor.28 , 29 See Ginkgo biloba under Spontaneous subdural hematoma.
Ginseng (Panax ginseng) has also been found to have antiplatelet activity through thromboxane inhibition and platelet-activating factor.30
Some authors also advocate cautious use of ginger and vitamin E when planning surgery, but the exact antiplatelet mechanism is unclear.25
Enoxaparin (Lovenox, Sanofi Aventis) (a LMWH)
Fondaparinux (Arixtra, GlaskoSmithKline)
Warfarin (Coumadin, Bristol-Myers Squibb)
Vitamin K 10mg IV x 3 days and/or PCC (25–100 UI/kg) or FFP (15 ml/kg)b 31
Dabigatran (Pradaxa®, Boehringer Ingelheim)
1–2 days, longer if renal CrCl <50 ml/min (see Table 9.5)
Rivaroxaban (Xarelto®, Bayer HealthCare)
24 hrs (see Table 9.5)
Apixaban (Eliquis®, Bristol-Myers Squibb)
48 hrs (see Table 9.5)
Antithrombin, recombinant (ATryn, Lundbeck)
Antithrombin III (Thrombate III, Grifols)
Dalteparin (Fragmin, Eisai)
Bivalirudin (Angiomax®, The Medicines Company)
Desirudin (Iprivask®, Canyon)
CrCl < 60 use caution, decrease initial dose31
Abbreviations: PCC = prothrombin complex concentrate, IV = intravenous, SQ = subcutaneous, aPTT = partial thromboplastin time, DVT = deep venous thrombosis, HIT = heparin induced thrombocytopenia, ACT = activated clotting time, AT = anti-thrombin, CrCl = creatinine clearance
b Intravenous vitamin K has a more rapid onset than subcutaneous vitamin K and current formulations, made with micelles of lecithin and glycol, seem to have a lower complication profile than older formulations containing polyethylated castor oil.36
The recommended minimum interval between last dose and procedure is based on renal function and procedure risk. Generally, neurosurgical procedures including minor procedures such as LPs are considered interventions with a high bleeding risk
Aspirin (Acetylsalicylic acid)
Clopidogrel (Plavix®, Sanofi Aventis)
Ticlodipine (Ticlid, Roche)
Prasugrel (Effient®, Eli Lilly)
Used for coronary artery disease31
Ticagrelor (Brilinta, AstraZeneca)
Dipyridamole (Persantine, Boehringer Ingelheim)
Abciximab (ReoPro, Eli Lilly)
Platelet function returns to ≈50% of baseline 24hrs after infusion; low-level inhibition may continue for up to 7 weeks32
Eptifibatide (Integrilin, Millennium/Merck)
CrCl<50 adjust infusion rate; platelet function returns to ≈50% 4hrs after infusion D/C’d32
Triofiban (Aggrastat, Medicure)
CrCl<30 adjust infusion rate; platelet coagulation is inhibited within 5 min, and remains inhibited for 3–8h32
Abbreviations: PCC = prothrombin complex concentrate, IV = intravenous, SQ = subcutaneous, aPTT = partial thromboplastin time, ACT = activated clotting time, CrCl = creatinine clearance, D/C = discontinue
b Desmopressin enhances platelet adhesion to vessel wall by increased concentrations of factor VIII and von Willebrand factor. Desmopressin increased platelet adhesion in randomized trial in both aspirin group and control group.38
See also platelet function inhibitors.
An oral vitamin K antagonist. To anticoagulate average weight patient, give 10 mg PO q d × 2–4 days, then ≈ 5 mg q d. Follow coagulation studies, titrate to PT = 1.2–1.5 × control (or INR ≈ 2–3) for most conditions (e.g. DVT, single TIA). Higher PT ratios of 1.5–2 × control (INR ≈ 3–4) may be needed for recurrent systemic embolism, mechanical heart valves… (the recommended ranges for the International Normalized Ratio (INR) are shown in Table 9.7).
Starting warfarin: During the first ≈ 3 days of warfarin therapy, patients may actually be hypercoagulable (secondary to reduction of vitamin-K dependent anticoagulation factors protein C and protein S), putting them at risk of “Coumadin necrosis.” Therefore patients should be “bridged” by starting either Lovenox which can be self-administered as an outpatient, or heparain (with a therapeutic PTT).
℞ Full anticoagulation in an average weight patient, give 5000 U bolus IV, follow with 1000 U/hr IV drip. Titrate to therapeutic anticoagulation of APTT = 2–2.5 × control (for DVT, some recommend 1.5–2 × control41 ).
℞ prophylactic AKA low-dose (“mini-dose”) heparin: 5000 IU SQ q 8 or 12 hrs. Routine monitoring of APTT is usually not done, although occasionally patients may become fully anticoagulated on this regimen.
Side effects: (see Anticoagulant considerations in neurosurgery above): hemorrhage, thrombosis42 (heparin activates anti-thrombin III and can cause platelet aggregation) which can result in MIs, DVTs, PEs, strokes, etc. Heparin induced thrombocytopenia (HIT): transient mild thrombocytopenia is fairly common in the first few days after initiating heparin therapy, however severe thrombocytopenia occurs in 1–2% of patients receiving heparin > 4 days (usually has a delayed onset of 6–12 days, and is due to consumption in heparin-induced thrombosis or to antibodies formed against a heparin-platelet protein complex). The incidence of HIT in SAH is 5–6% and was similar with enoxaparin.43 Consider use of fondaparinux in thrombocytopenic patients. Chronic therapy may cause osteoporosis.
Low molecular weight heparins (LMWH) (average molecular weight = 3000–8000 daltons) are derived from unfractionated heparin (average MW = 12,000–15,000 daltons). LMWHs differ from unfractionated heparin because they have a higher ratio of anti-factor Xa to anti-factor IIa (antithrombin) activity which theoretically should produce antithrombic effects with fewer hemorrhagic complications. Realization of this benefit has been very minor in clinical trials. LMWH have greater bioavailability after sub-Q injection leading to more predictable plasma levels which eliminates the need to monitor biologic activity (such as APTT). LMWH have a longer half-life and therefore require fewer doses per day. LMWH have a lower incidence of thrombocytopenia. More effective in DVT prophylaxis than warfarin in orthopedic surgery.46
Spinal epidural hematomas: There have been a number of case reports of spinal epidural hematomas occurring in patients on LMWH (primarily enoxaparin) who also underwent spinal/epidural anesthesia or lumbar puncture, primarily in elderly women undergoing orthopedic surgery. Some have had significant neurologic sequelae, including permanent paralysis.47 The risk is further increased by the use of NSAIDs, platelet inhibitors, or other anticoagulants, and with traumatic or repeated epidural or spinal puncture.
Available low molecular weight heparins
Reversal of anticoagulation: Praxbind (idarucizumab) IV for emergencies. Reverses pradaxa within 4 hrs, lasts 24 hrs.48
A synthetic analog of the pentasaccharide binding sequence of heparin. Increases factor Xa inhibition without affecting factor IIa (thrombin).49 Unlike heparin, fondaparinux does not bind to other plasma proteins or platelet factor-4 and does not cause heparin-induced thrombocytopenia (HIT) and can therefore be used in patients with HIT. May be more effective than enoxaparin (Lovenox®) for preventing post-op DVTs. Side effects: Bleeding is the most common side effect (may be increased by concurrent NSAID use). ✖ Contraindicated with severe renal impairment (CrCl < 30 ml/min).50
℞: 2.5 mg SQ injection q d. Supplied: 2.5 mg single-dose syringes. Pharmacokinetics: Peak activity occurs in 2–3 hrs. Half-life: 17-21 hrs. Anticoagulation effect lasts 3-5 half-lives. Elimination: in urine (in renal insufficiency reduce dose by 50% for CrCl 30-50 ml/min). STOP: 2-4 days pre-op (longer with kidney dysfunction)
Warfarin induced anticoagulation may be reversed up to 4 or 5 times more quickly with PCC (Kcentra) (contains coag factors II, IX, and X) than with FFP.51 Patient may become hyperthrombotic with this.
To reverse elevated PT from warfarin , give aqueous colloidal solution of vitamin K1 (phytonadione, Mephyton®). Doses > 10 mg may produce warfarin resistance for up to 1 week. FFP may be administered concurrently for more rapid correction (see above). See recommended levels of PT.
IV administration has been associated with severe reactions (possibly anaphylactic), including hypotension and even fatalities (even with proper precautions to dilute and administer slowly), therefore IV route is reserved only for situations where other routes are not feasible and the serious risk is justified. ℞ IV (when IM route not feasible): 10–20 mg IV at a rate of injection not to exceed 1 mg/min (e.g. put 10 mg in 50 ml of D5W and give over 30 minutes).
Enoxaparin (Lovenox®): ≈ 60% of Lovenox can be reversed with 1mg of protamine for every mg of Lovenox given (maximum dose = 50 mg) within the last 8 hrs, and 0.5 mg of protamine for every mg of Lovenox given from 8–12 hrs prior. Protamine is probably not needed for Lovenox given > 12 hrs earlier.
Dalteparin (Fragmin®) or ardeparin (Normiflo®): 1 mg of protamine for every 100 anti-Xa IU of the LMWH (maximum dose = 50 mg) with a second infusion of 0.5 mg protamine for every 100 anti-Xa IU of LMWH if the APTT remains elevated 2–4 hours after the first dose is completed.
Causes an increase in factor III coagulant activity and von Willebrand factor which helps coagulation and platelet activity in hemophilia A and in von Willebrand’s disease Type I (where the factors are normal in makeup but low in concentration, ✖ but may cause thrombocytopenia in von Willebrand’s disease Type IIB where factors may be abnormal or missing).
Abnormal intravascular coagulation which consumes clotting factors and platelets, coupled with abnormal activation of fibrinolytic system. Head trauma is an independent risk factor for DIC, possibly because the brain is rich in thromboplastin which may be released into systemic circulation with trauma.52 Other risk factors: shock, sepsis.
anticoagulants, if not contraindicated
DVT is of concern primarily because of the potential for material (clot, platelet clumps…) to dislodge and form emboli (including pulmonary emboli, (PE)) which may cause pulmonary infarction, sudden death (from cardiac arrest), or cerebral infarction (from a paradoxical embolus, which may occur in the presence of a patent foramen ovale, see Cardiogenic brain embolism). The reported mortality from DVT in the LEs ranges from 9–50%.53 DVT limited to the calf has a low threat (< 1%) of embolization, however, these clots later extend into the proximal deep veins in 30–50% of cases,53 from where embolization may occur (in 40–50%), or they may produce postphlebitic syndrome.
in patients with brain tumors (see below) or head injury54
Specific “neurological” risk factors for DVT and PE include53 :
neurosurgical operation: risk is higher following craniotomy for supratentorial tumors (7% of 492 patients) than p-fossa tumors (0 out of 141)57
pneumatic compression boots58 (PCBs) or sequential compression devices (SCDs): reduces the incidence of DVTs and probably PEs. Do not use if DVTs already present. Continue use until patient able to walk 3–4 hrs per day
TED Stockings®: (TEDS) applies graduated pressure, higher distally. As effective as PCB. No evidence that the benefit is additive.53 Care should be taken to avoid a tourniquet effect at the proximal end (note: TEDS® is a registered trademark. “TED” stands for thromboembolic disease)
anticoagulation; see also contraindications and considerations of anticoagulation in neurosurgery
full anticoagulation is associated with perioperative complications59
“low-dose” anticoagulation60 ( low-dose heparin): 5000 IU SQ q 8 or 12 hrs, starting 2 hrs pre-op or on admission to hospital. Potential for hazardous hemorrhage within brain or spinal canal has limited its use
low molecular weight heparins and heparinoids: not a homogeneous group. Efficacy in neurosurgical prophylaxis has not been determined
combination of PCBs and “mini-dose” heparin starting on the morning of post-op day 1 (with no evidence of significant complications)61
Recommended prophylaxis varies with the risk of developing DVT, as illustrated in Table 9.8.53 See also details of prophylaxis in cervical spinal cord injuries.
(For PE, see below). The clinical diagnosis of DVT is very unreliable. A patient with the “classic signs” of a hot, swollen, and tender calf, or a positive Homans’ sign (calf pain on dorsiflexion of the ankle) will have a DVT only 20–50% of the time.53 50–60% of patients with DVT will not have these findings.
Doppler ultrasound with high-resolution real-time B-mode imaging: 95% sensitive and 99% specific for proximal DVT. Less effective for calf DVT.62 As a result, it is recommended that patients with initially negative studies undergo repeat studies over the next 7–10 days to R/O proximal extension. Requires more skill on the part of the tester than IPG. May be used in immobilized or casted LE (unlike IPG). Widely accepted as the non-invasive test of choice for DVT63
impedance plethysmography (IPG): looks for reduced electrical impedance produced by blood flow from the calf following relaxation of a pneumatic tourniquet. Good in detecting proximal DVT, not sensitive for calf DVT. A positive study indicates DVT that should be treated, a negative study can occur with non-occlusive DVT or with good collaterals, and should be repeated over a 2 week period
125I-fibrinogen: radiolabeled fibrinogen is incorporated into the developing thrombus. Better for calf DVT than proximal DVT. Expensive, and many false positives. Risk of HIV transmission has resulted in withdrawal of use
D-dimer (a specific fibrin degradation product): high levels are associated with DVT and PE64
unless anticoagulation is contraindicated: start heparin as outlined in Anticoagulation, aim for APTT = 1.5–2 × control; or fixed dose of LMW heparinoids, e.g. tinzaparin (Logiparin®,65 or in the U.S. enoxaparin (Lovenox®). Simultaneously initiate warfarin therapy. Heparin can be stopped after ≈ 5 days66
Post-op PE generally occurs 10–14 days following surgery.68 The reported incidence68 ranges from 0.4–5%. A series (on a service with routine use of elastic stockings and, in high risk patients, “mini-dose” heparin) found a post-op incidence of ≈ 0.4%, with a doubling of this number if only patients with major pathology (brain tumor, head trauma, or cerebrovascular or spinal pathology) were considered68 (another series dealing only with brain tumors found a 4% incidence57 ).
Common findings: sudden dyspnea (the most frequent finding), tachypnea, tachycardia, fever, hypotension, 3rd or 4th heart sound. Triad (rare): hemoptysis, pleuritic chest pain, dyspnea. Auscultation: pleuritic friction rub or rales (rare). Shock and CHF (mimics MI) indicates massive life-threatening PE. Mortality reported ranges from 9–60%,68 with a significant number of deaths within the first hour.
Alternatively, one can check for DVT utilizing IPG, Doppler, or venography (see above). If positive, this indicates a possible source of PE, and since the treatment is similar for both, no further search for PE need be made and treatment is started. If negative, further testing may be needed (e.g.VQ scan, see below).
ventilation-perfusion scan (VQ scan): CXR is also needed. A perfusion defect with no ventilation defect in a patient with no previous history of PE strongly suggests acute PE. Equivocal studies occur when an area of malperfusion corresponds to an area of reduced ventilation (on ventilation scan) or infiltrate (on CXR). Probabilities of PE based on VQ scan are shown in Table 9.9.70 A technically adequate normal VQ scan virtually rules out PE. Patients with low or intermediate probability scans should have a test for DVT or quantitative D-dimer (see above). If test for DVT is positive, treat; if it is negative, the choice is to follow serial IPG or Doppler studies for 2 weeks, or (rarely) to do a pulmonary angiogram
If diagnosis is seriously entertained, start heparin – unless contraindicated – without waiting for results of diagnostic studies. For an average 70 kg patient, begin with 5000–7500 unit IV bolus, followed by 1000 U/hr drip (less for smaller patient). Follow PTT and titrate drip rate for PTT 1.5 to 2 × control.
In chronic anemias (especially thalassemia major, AKA Cooley’s anemia), low hematocrit results in chronic over-stimulation of bone marrow to produce RBCs. This results in systemic bony abnormalities, cardiomyopathy (due to hemochromatosis caused by increased breakdown of defective RBCs).
vertebral bodies: may result in epidural cord compression71 (see below)
Surgical excision followed by radiation therapy has been the recommended treatment. Repeated blood transfusions may help reduce EMH and may be useful post-op instead of RTX except for refractory cases.71
1 Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med. 2000;160:1630-1638.
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