# Presentation: 028827

## Thrombosis Risk-Assessment As A Guide To Thrombosis Prophylaxis In Surgical Patients

**Joseph A. Caprini, M.D., M.S., FACS, RVT, FACPh**
**Louis W. Biegler Professor of Surgery and Bioengineering**
**Department of Surgery, Evanston Northwestern Healthcare, Evanston, IL **
**Northwestern University, The Feinberg School of Medicine, Chicago, IL**
**Robert R. McCormick School of Engineering and Applied Sciences,**
**Northwestern University, Evanston, IL**

## Levels Of Thromboembolism Risk In Surgical Patients Without Prophylaxis

**Levels Of Thromboembolism Risk In Surgical Patients Without Prophylaxis**

| Level of risk | Calf DVT, % | Proximal DVT, %  | Clinical PE, %  | Fatal PE, %  |
| --- | --- | --- | --- | --- |
| Moderate | 10–20 | 2–4 | 1–2 |    0.1–0.4 |
| Low | 2 | 0.4 | 0.2 |  < 0.01  |

## Levels Of Thromboembolism Risk In Surgical Patients Without Prophylaxis

**Levels Of Thromboembolism Risk In Surgical Patients Without Prophylaxis**

| Level of risk | Calf DVT, % | Proximal DVT, %  | Clinical PE, %  | Fatal PE, %  |
| --- | --- | --- | --- | --- |
| Highest | 40–80 | 10–20 |   4–10 | 0.2–5 |
| High | 20–40 | 4–8 | 2–4 |    0.4–1.0 |

##  “ACCP Guideline-Defined” Risk of Venous Thromboembolism in Y2002 (hospital discharges)

- Highest risk surgery		     744,465
- High risk surgery		  3,031,318
- Moderate risk surgery		  2,019,696
- _Surgical total__	__	__  5,795,479_

- 13,392,124 / 37,804,021 =  35% of all hospital discharges

- Anderson, FA., et al. ASH, 2005

## VTE Incidence

**Surgical ****	****	****	****	****	**
**Moderate risk ****	****	****  5.2 ****	****      ****	****         2.7 ****	**
**High risk ****	****	****10.3 ****	****      ****	****         5.4 ****	**
**Highest risk ****	**** ****	****24.1 ****	****    ****	****       12.6**

**                       ****Probability of Pulmonary Emboli (%) **
**              ****Without prophylaxis      With prophylaxis**
**                                  **_**%**_**                                  **_**%**_
**                                                                                                                                                                                   ****	****	****     ****PE                                PE **

**  ****Prophylaxis utilization**
**  **_**%**_
** **
-  **40 **
** ****65 **
** ****85 **

**Given that effective VTE prophylaxis and expert consensus prophylaxis guidelines are widely available, these data suggest that universal safe and effective prophylaxis could significantly reduce US VTE incidence and related deaths.**

**The majority (93%) of estimated VTE-related deaths in the US were due to  sudden, fatal PE (34%)  and 59% of these fatalities were in those with undiagnosed VTE (59%).**

_**VTE Incidence**_

**Heit, JA et al. ASH, 2005**

## Fatal Pulmonary Embolism

**Fatal Pulmonary Embolism**

- Randomized double-blind comparison of LMWH with UFH, involving 23,078 patients, 73.9% of whom underwent general surgery

|  | LMWH (N = 11,542)
 N    (%) | UFH (N = 11,536)
N    (%) | p |
| --- | --- | --- | --- |
| PE (at autopsy) | 22  (0.191) | 22  (0.191) |  |
| Fatal | 17  (0.147) | 18  (0.156) | 0.87 |
| Non-fatal |   5  (0.043) |   4  (0.035) | 1 |

**Haas S, et al. Thromb Haemost. 2005;94:814-9.**

## It Takes 13 days at 900 departures/day to equal 11,700 flights which means 17 crashes at Ohare every 13 days--- or more than one daily

## Patient Intake Form

**Personal History of DVT or PE**
**2.    Family History of DVT or PE**
**3.    Malignancy:  Current or Previous**
**4.    Personal History of Recent MI or  stroke (**_**<**_** 1 month)**
**Recent Major Surgery (**_**<**_** 1 month)**
**6.  Currently on BCP, HRT, or hormonal**
**      ****therapy for Breast or Prostate Cancer**
**7.  Current or recent acute inflammatory or**
**      ****infectious process (**_**<**_** 1 month)**
**8. Currently immobile (unable to ambulate**
**     ****in the in-patient setting)****	**
**9.  History of unexplained stillborn infant, **
**     ****recurrent spontaneous abortion.premature**
**    ****birth with preeclampsia or growth-restricted**
**    ****infant. ****	****	****	****	**
**10. Swollen legs ****	****	****	**
**11. Varicose Veins****	****	****	**
**12. Obesity (BMI **_**>**_** 30)****	****	**
**13.  Age****	****	**

**Patient Intake Form**

**Physician Assessment**

## SUBCUTANEOUS LOW-DOSE UNFRACTIONATED HEPARIN

**SUBCUTANEOUS LOW-DOSE UNFRACTIONATED HEPARIN**

**Kakkar Lancet, 1975; Collins NEJM, 1988**

**Efficacy and safety validated in 98 centers and 20,000 patients over a 13 year period when control groups and venographic confirmation were allowed**

## Comparison of 16 Clinical Trials 

**Comparison of 16 Clinical Trials **

- Data from 16 clinical trials conducted 1980-2003
- Trials selected based on initial computerized literature search including PubMed, EMBASE
- Compared LMWH vs UFH, placebo, or other LMWH
- No formal statistical meta-analysis performed
**	****Conclusions:**
- Patients undergoing abdominal surgery should be stratified by risk for thromboembolism and managed accordingly
- LMWH is a recommended alternative to UFH in moderate- or high-risk patients
- In patients with cancer:
- High-dose LMWH may offer increased benefits without increased bleeding
- Extended 4-week period of prophylaxis appears beneficial

- Bergqvist D. *Br J Surg*. 2004;91:965-974.

***VTE Prophylaxis After Abdominal Surgery***

**Notes:**
Bergqvist and colleagues compared data from 16 randomized comparative clinical trials conducted between 1980 and 2003 of low-molecular-weight heparin (LMWH) used in patients undergoing general abdominal surgery (9/16), abdominal cancer surgery (5/16), or colorectal surgery (2/16)1 
The initial computerized literature search was conducted to identify English language articles and scanned the PubMed and EMBASE databases using the specific terms “heparin,” “surgery,” “abdominal or rectal or colorectal or rectum or colon,” and “clinical trial”
Other articles were identified through the Cochrane Library database and the reference lists of papers found in the primary literature search. Potential studies identified as comparative trials of LMWH in abdominal surgery were selected from the literature search
Because of the heterogeneity of design, including end points, no formal statistical meta-analysis of the 16 trials was conducted
Bergqvist reached these conclusions1:
Patients undergoing abdominal surgery should be stratified according to risk for thromboembolism and managed accordingly
LMWH is a recommended alternative to UFH in moderate- or high-risk patients
In patients with cancer:
High-dose LMWH may offer increased protection against thrombosis without increased risk of bleeding
An extended 4-week period of prophylaxis appears beneficial

## Venous Thromboembolism Prophylaxis Following Orthopedic Procedures

**Venous Thromboembolism Prophylaxis Following Orthopedic Procedures**

| Type Of Procedure | Patients | Pentasaccharide | LMWH |
| --- | --- | --- | --- |
| Total Hip Replacement Europe, etc. ( 22 countries) | 1723 | 4.1%* | 9.2% |
| Total Hip Replacement North America | 2257 | 6.1% | 8.3% |
| Total Knee Replacement | 1034 | 12.5%* | 27.8% |
| Hip Fracture Repair | 1711 | 8.3%* | 19.1% |

***p<.0001**

| Extended Hip
Fracture Repair
Venogram=30 day | 426 | 7 days Fondaparinux
35% | 30 Days Fondaparinux
1.4%*  |
| --- | --- | --- | --- |

## VTE Prophylaxis In General Surgery

**VTE Prophylaxis In General Surgery**

- Lowest venographic DVT rate ever seen in general surgery

**ISTH Aug, 2005**

**Combined Modalities**

## Fondaparinux: Major Bleeding Up to Day 11 By Study

- **P*=0.006 for Fondaparinux vs enoxaparin for major bleeding up to 11 days after major knee surgery; major bleeding included bleeding that was fatal, retroperitoneal, intracranial, intraspinal, in a critical organ, led to reoperation, or had a bleeding index 2.

- 1. Bauer KA et al. *N Engl J Med.* 2001;345:1305-1310.
- 2. Lassen MR et al. *Lancet.* 2002;359:1715-1720.
- 3. Turpie AGG et al. *Lancet. *2002;359:1721-1726.
- 4. Eriksson BI et al. *N Engl J Med.* 2001;345:1298-1304.

*****

**2**

**3**

**4**

**1**

**      ****NS**

***Bleeding With a Positive BI Largely Accounts for Higher Bleeding Incidence**

## Intermittent Pneumatic Compression And Deep Vein Thrombosis PreventionA meta-analysis in postoperative patients

- A total of 2,270 patients were included in 15 eligible studies: 1,125 in the IPC group and 1,145 in the no prophylaxis group.
- IPC devices reduced the risk of DVT by 60% (relative risk 0.40, 95% CI 0.29 – 0.56; p< 0.001)
- The authors suggest that further randomized trials are warranted to test the utility of IPC in hospitalized medical patients as well as combination pharmacological-IPC prophylaxis in both medical and surgical patients.

**Urbanakova,J et al.** **Thromb Haemost 2005; 94: 1-5**

**Combined Modalities**

## When to Think About Pneumatic Compression

**Patients with 2-3 risk factors**
**Patients with >4 risk factors in combination with anticoagulant prophylaxis**
**Patients with hemostatic defects like hemophilia, Von Willebrand’s disease,  platelet functional defects, heparin induced thrombocytopenia, etc**
**Patients with bleeding disorders, bleeding ulcers, bleeding from colitis or ileitis, acute hemorrhagic stroke. **
**Patient needing craniotomy or spinal cord surgery. **
**Patients requiring complex cancer operations associated with large blood loss such as a pancreatoduodenectomy, major hepatic resection, or extensive pelvic resection, etc.**
**Patients with closed head injuries, pelvic hematomas, and/or other complex trauma situations. **

## Conclusions

- Individual risk assessment key to appropriate prophylaxis
**IPC is very effective for those who have 2-4 risk factors**
- Combined physical and pharmacologic methods appropriate for the highest-risk individuals
- UFH is effective but relatively high incidence of HIT, poor anticancer effects, and difficult outpatient use are problems
- LMWH offers greater effectiveness, lower HIT incidence, good anticancer effects, and excellent 30 day postoperative efficacy
- Fondaparinux offers excellent efficacy, no worry about HIT, the lowest reported incidence of DVT  in hip, knee, and hip fracture patients. Early data show the lowest DVT rates in  abdominal surgery cancer patients especially when combined with IPC.