Inferior Vena Cava (IVC) Filters and Haptoglobin Level Matthew Elkins M.D. Ph.D., Laura Cooling...
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Inferior Vena Cava (IVC) Filters and Haptoglobin Level Inferior Vena Cava (IVC) Filters and Haptoglobin Level Matthew Elkins M.D. Ph.D., Laura Cooling M.D., M.S., Donald Giacherio Ph.D. University of Michigan Health System, Ann Arbor, Michigan Introduction Methods Results Conclusions Low serum haptoglobin levels are often utilized as a marker for acute intravascular immune hemolysis (Levy et al. 2009). However, any state resulting in hemolysis will result in decreased serum haptoglobin. Our index patient was a 52 year old man with a positive DAT (IgG+, eluate negative) and conflicting laboratory findings of hemolysis. Although the patient had a stable hemoglobin, normal LDH and bilirubin, he had an extremely low haptoglobin (<10 mg/dL). His past medical history was significant for several DVTs requiring placement of an inferior vena cava (IVC) filter (Fig. 1). We posited that the low serum haptoglobin level in this patient may be due to chronic low-level shear hemolysis at the level of the IVC filter. A literature search showed no prior investigations into the effect of IVC filter placement on serum haptoglobin levels. Twenty-two patients were investigated for a change in serum haptoglobin levels following placement of an IVC filter. Serum haptoglobin levels were obtained immediately prior to IVC placement and then daily over a period of 3-14 days. Serum haptoglobin was measured by an immunoturbidimetric assay on a Roche COBAS Integra 800 automated chemistry analyzer (Roche Diagnostics Corporation, Indianapolis, IN). In this assay, haptoglobin forms immune complexes with specific anti-human haptoglobin antisera, and the increase in turbidity is detected at 340 nm. Both the absolute and relative (%) change in haptoglobin from pre-IVC baseline were determined for each patient. Patients with >50% decrease in haptoglobin were examined separately. Significance was determined by student t-test (2-tailed, paired). Both graphics and statistics were performed with commercial software (Kaliedograph, Synergy Software). This study suggests that up to 20% (3/20) patients can experience a significant drop in haptoglobin following IVC filter placement. The presence of an IVC filter should be considered when evaluating causes of a low serum haptoglobin 0 0.5 1 1.5 2 2.5 3 3.5 4 0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 450 480 510 540 570 N o.Patients Pre-O p H aptoglobin (m g/dL,D ay 0) x = 233.8 + 163.5 0 100 200 300 400 500 600 G roup 1 Pt1 Pt2 Pt3 H aptoglobin (m g/dL) 0 7 14 NS NS 0 7 14 0 7 14 0 7 14 D ay 43% 2% 20% 41% 0 50 100 150 200 250 1 3 5 14 % P re-O p H aptoglobin Post-O p D ay p = 0.02 0 (Pre-O p) G roup 1 G roup 2 Figure 1. IVC filter placed into the patients on this study. The Gunther Tulip IVC Filter (a model of the “Greenfield” venous filter). Image from Cook Medical. Figure 2. Distribution of serum haptoglobin levels in patients immediately prior (Day 0) to placement of an IVC filter. Figure 3. Relative percent change in serum haptoglobin following IVC filter placement in 20 patients. Group 1: 17/20 patients with no significant decrease in haptoglobin (mean + SE). Group 2: 3 patients with a > 50% decrease in haptoglobin at 7 days. Figure 4. Comparison of the absolute serum haptoglobin at baseline, 7, and 14 days following IVC placement. Shown are Group I (mean + SD) and all 3 patients in Group 2. The percent baseline haptoglobin also shown. NS, not significant Hct* transfusio ns bleeding infection surgery thrombolys is Bilirub in* AST* LDH* 1 33.2 none no no no no ND ND ND 2 26.7 Day 1: 3u RBCs Day 2: 1u RBC no yes, infected incision no yes, Day 0 0.6 38 ND 3 28.8 none no yes; MSSA line sepsis no no ND ND ND 4 35 Day 6: 3u RBCs Ongoing widening of aneurysm no Day 6: IR stent placed no 0.2 17 ND 5 29.3 Day 0: 2u RBCs Day 1: 2u RBCs Day 1: melena yes; UTI and sepsis no no ND ND ND 6 29.8 Day 1: 2u RBCs Post-surgical DVT no Day -1 spinal fusion no 0.5 71 ND 7 24.7 Day 2: 2u RBCs no Osteomyelitis Day 2: spinal decompression no 0.2 11 ND 8 29 Day 13: 2u RBCs no yes; Cdiff no no 15.8 225 464 9 34.3 Day 0: 4u RBCs no yes; PNA no no 0.6 49 ND Table 1: Possible confounding causes of haptoglobin decrease in 9 patients followed for 1-2 weeks after IVC filter placement. Group 2 (Pts 1-3) shown in yellow. *Labs values from day 6 or 7. References •Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman, Anbinder Y, Lache O, Nakhoul FM, Asaf R, Farbstein D, Pollak M, Soloveichik YZ, Strauss M, Alshiek J, Livshits A, Schwartz A, Awad H, Jad H, Goldenstein H. 2009. Haptoglobin: basic and clinical aspects. Antioxidants & Redox signaling [Epub] •Mecozzi G, Milano AD, De Carlo M, Sorrentino F, Pratali S, Nardi C, Bortolotti U. 2002 •Cook Medical - cookmedical.com Baseline Haptoglobin Levels Pre-IVC haptoglobin levels ranged widely between individuals (Fig. 2), including 2 individuals with haptoglobins of 2 and 4 mg mg/dL each. These 2 individuals were excluded from further analysis. Haptoglobin Levels After IVC placement In the majority of patients (Group 1, Fig. 3), haptoglobin levels rose immediately following IVC placement, consistent with an acute phase response. There was a significant rise in the first 24 hours (p=0.026), which continued to slowly rise over the first 7 days (6/6 patients). By the end of 2 weeks, haptoglobin levels tended to decrease toward baseline levels although haptoglobin levels remained elevated (Fig. 4). In contrast to Group 1, 3 patients demonstrated a > 50% decrease in haptoglobin over the first 7 days following IVC placement (Group 2, Fig 3). In Group 2, the relative decrease in haptoglobin ranged from 57%- 80% (p = 0.02, Fig 4). A 14 day sample was available in 1 patient (Pt 1). As shown, the haptoglobin continued to fall, decreasing 98% of baseline levels. By the end of 2 weeks, the absolute haptoglobin in this patient was abnormal (5 mg/dL, Fig. 4) suggestive of intravascular hemolysis. Results Chart Review for Causes of Low Haptoglobin Nine patients from Group 1 (4-9) and Group 2 (1-3) were examined for potential causes of low haptoglobin including liver dysfunction, bleeding, transfusions, infection, surgery, and thrombolysis (Table 1). There was no correlation between specific clinical factors and low haptoglobin between the two groups.
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Transcript of Inferior Vena Cava (IVC) Filters and Haptoglobin Level Matthew Elkins M.D. Ph.D., Laura Cooling...
Inferior Vena Cava (IVC) Filters and Haptoglobin LevelInferior Vena Cava (IVC) Filters and Haptoglobin Level Matthew Elkins M.D. Ph.D., Laura Cooling M.D., M.S., Donald Giacherio Ph.D.
University of Michigan Health System, Ann Arbor, Michigan
Introduction
Methods
Results
Conclusions
Low serum haptoglobin levels are often utilized as a marker for acute intravascular immune hemolysis (Levy et al. 2009). However, any state resulting in hemolysis will result in decreased serum haptoglobin. Our index patient was a 52 year old man with a positive DAT (IgG+, eluate negative) and conflicting laboratory findings of hemolysis. Although the patient had a stable hemoglobin, normal LDH and bilirubin, he had an extremely low haptoglobin (<10 mg/dL). His past medical history was significant for several DVTs requiring placement of an inferior vena cava (IVC) filter (Fig. 1). We posited that the low serum haptoglobin level in this patient may be due to chronic low-level shear hemolysis at the level of the IVC filter. A literature search showed no prior investigations into the effect of IVC filter placement on serum haptoglobin levels.
Twenty-two patients were investigated for a change in serum haptoglobin levels following placement of an IVC filter. Serum haptoglobin levels were obtained immediately prior to IVC placement and then daily over a period of 3-14 days. Serum haptoglobin was measured by an immunoturbidimetric assay on a Roche COBAS Integra 800 automated chemistry analyzer (Roche Diagnostics Corporation, Indianapolis, IN). In this assay, haptoglobin forms immune complexes with specific anti-human haptoglobin antisera, and the increase in turbidity is detected at 340 nm. Both the absolute and relative (%) change in haptoglobin from pre-IVC baseline were determined for each patient. Patients with >50% decrease in haptoglobin were examined separately. Significance was determined by student t-test (2-tailed, paired). Both graphics and statistics were performed with commercial software (Kaliedograph, Synergy Software).
This study suggests that up to 20% (3/20) patients can experience a significant drop in haptoglobin following IVC filter placement. The presence of an IVC filter should be considered when evaluating causes of a low serum haptoglobin
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No.
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Pre-Op Haptoglobin (mg/dL, Day 0)
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% P
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0(Pre-Op)
Group 1
Group 2
Figure 1.IVC filter placed into the patients on this study. The Gunther Tulip IVC Filter (a model of the “Greenfield” venous filter). Image from Cook Medical.
Figure 2.Distribution of serum haptoglobin levels in patients immediately prior (Day 0) to placement of an IVC filter.
Figure 3.Relative percent change in serum haptoglobin following IVC filter placement in 20 patients. Group 1: 17/20 patients with no significant decrease in haptoglobin (mean + SE). Group 2: 3 patients with a > 50% decrease in haptoglobin at 7 days.
Figure 4.Comparison of the absolute serum haptoglobin at baseline, 7, and 14 days following IVC placement. Shown are Group I (mean + SD) and all 3 patients in Group 2. The percent baseline haptoglobin also shown. NS, not significant
Hct* transfusions bleeding infection surgery thrombolysis Bilirubin* AST* LDH*1 33.2 none no no no no ND ND ND
2 26.7 Day 1: 3u RBCs Day 2: 1u RBC no yes, infected incision no yes, Day 0 0.6 38 ND
3 28.8 none no yes; MSSA line sepsis no no ND ND ND
4 35 Day 6: 3u RBCs Ongoing widening of aneurysm no Day 6: IR stent placed no 0.2 17 ND
5 29.3 Day 0: 2u RBCs Day 1: 2u RBCs Day 1: melena yes; UTI and sepsis no no ND ND ND
6 29.8 Day 1: 2u RBCs Post-surgical DVT no Day -1 spinal fusion no 0.5 71 ND
7 24.7 Day 2: 2u RBCs no Osteomyelitis Day 2: spinal decompression no 0.2 11 ND
8 29 Day 13: 2u RBCs no yes; Cdiff no no 15.8 225 464
9 34.3 Day 0: 4u RBCs no yes; PNA no no 0.6 49 ND
Table 1: Possible confounding causes of haptoglobin decrease in 9 patients followed for 1-2 weeks after IVC filter placement. Group 2 (Pts 1-3) shown in yellow. *Labs values from day 6 or 7.
References•Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman, Anbinder Y, Lache O, Nakhoul FM, Asaf R, Farbstein D, Pollak M, Soloveichik YZ, Strauss M, Alshiek J, Livshits A, Schwartz A, Awad H, Jad H, Goldenstein H. 2009. Haptoglobin: basic and clinical aspects. Antioxidants & Redox signaling [Epub]•Mecozzi G, Milano AD, De Carlo M, Sorrentino F, Pratali S, Nardi C, Bortolotti U. 2002 •Cook Medical - cookmedical.com
Baseline Haptoglobin LevelsPre-IVC haptoglobin levels ranged widely between individuals (Fig. 2), including 2 individuals with haptoglobins of 2 and 4 mg mg/dL each. These 2 individuals were excluded from further analysis.
Haptoglobin Levels After IVC placementIn the majority of patients (Group 1, Fig. 3), haptoglobin levels rose immediately following IVC placement, consistent with an acute phase response. There was a significant rise in the first 24 hours (p=0.026), which continued to slowly rise over the first 7 days (6/6 patients). By the end of 2 weeks, haptoglobin levels tended to decrease toward baseline levels although haptoglobin levels remained elevated (Fig. 4).
In contrast to Group 1, 3 patients demonstrated a > 50% decrease in haptoglobin over the first 7 days following IVC placement (Group 2, Fig 3). In Group 2, the relative decrease in haptoglobin ranged from 57%- 80% (p = 0.02, Fig 4). A 14 day sample was available in 1 patient (Pt 1). As shown, the haptoglobin continued to fall, decreasing 98% of baseline levels. By the end of 2 weeks, the absolute haptoglobin in this patient was abnormal (5 mg/dL, Fig. 4) suggestive of intravascular hemolysis.
Results
Chart Review for Causes of Low HaptoglobinNine patients from Group 1 (4-9) and Group 2 (1-3) were examined for potential causes of low haptoglobin including liver dysfunction, bleeding, transfusions, infection, surgery, and thrombolysis (Table 1). There was no correlation between specific clinical factors and low haptoglobin between the two groups.
