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 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*transfusionsbleedinginfectionsurgerythrombolysisBilirubin*AST*LDH* noneno ND Day 1: 3u RBCs Day 2: 1u RBC noyes, infected incisionnoyes, Day ND nonenoyes; MSSA line sepsisno ND 4 35Day 6: 3u RBCs Ongoing widening of aneurysm noDay 6: IR stent placedno0.217ND Day 0: 2u RBCs Day 1: 2u RBCs Day 1: melenayes; UTI and sepsisno ND Day 1: 2u RBCsPost-surgical DVTnoDay -1 spinal fusionno0.571ND Day 2: 2u RBCsnoOsteomyelitisDay 2: spinal decompressionno0.211ND 8 29Day 13: 2u RBCsnoyes; Cdiffno Day 0: 4u RBCsnoyes; PNAno 0.649ND 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 Haptoglobin: basic and clinical aspects. Antioxidants & Redox signaling [Epub] Mecozzi G, Milano AD, De Carlo M, Sorrentino F, Pratali S, Nardi C, Bortolotti U 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.