Contributions
Abstract: EP773
Type: E-Poster Presentation
Session title: Hodgkin lymphoma - Clinical
Background
Hodgkin lymphoma (HL) is characterized by an inflammatory syndrome, associated to advanced stages and B-symptoms and frequently manifested with increase in inflammation markers.
We observed in clinical practice, that HL patients frequently present at diagnosis with mild coagulation disorders, namely prolonged prothrombin time (PT) / INR and activated partial thromboplastin time (aPTT), which is not described as an established knowledge in textbooks.
Aims
We aimed to 1) analyze coagulation parameters [prothrombin time (PT), INR and activated partial thromboblastin time (aPTT)] in newly diagnosed HL patients in comparison to healthy individuals, 2) correlate them with clinical and laboratory parameters, and 3) investigate the possible underlying mechanisms.
Methods
Coagulation parameters (PT/INR, aPTT, fibrinogen, D-dimers) were determined and recorded in 80 consecutive patients with newly diagnosed HL before treatment initiation, compared to 225 healthy individuals and analyzed according to demographic data, clinical findings (histology, disease extent, IPS, B-symptoms) and laboratory parameters related to inflammation (hemoglobin, platelet and white blood cell count, ESR/CRP, albumin, α2/γ-globulins, ferritin/haptoglobin). Coagulation factors (F)II, V, VII, X and TFPI were measured in plasma and serum with ELISA, respectively, in 35/80 patients.
Results
HL patients demonstrated increased median values of all parameters compared to controls: INR 1.12 vs 0.99 (p<0.001), aPTT 37.8 vs 33.9 (p<0.001) and fibrinogen 587.5 vs 303 (p<0.001). INR was elevated (>1.2) in 28.7% of patients, aPTT (>40 sec) in 32.9%, fibrinogen (>400 mg/dL) in 83.3% and D-Dimers (>0.5 μg/ml) in 54.4%. Elevated INR/PT, aPTT, and fibrinogen were observed more frequently in patients with advanced stages (ΙΙΒ/ΙΙΙ/V) and B-symptoms. INR and aPTT correlated strongly with all inflammation markers (Spearman’s rho 0.25-0.53 and 0.26-0.38) except of leukocyte counts (and γ-globulins and ferritin for aPTT). Significantly increased levels of FII, FV and FX were observed in the majority of the patients (54.3%>88.6%), while FVII was found to be within normal limits and decreased in 1/35 patients. TFPI levels were also elevated in most cases (65.7%). A negative strong correlation between INR and FVII was noted (p<0.001). FII, FV, FX correlated with each other and with fibrinogen (p= 0.001-0.030), as well as with inflammation markers. No correlation was found between coagulation factor levels and clinical stage, B-symptoms or IPS, except the one of FX with high IPS (p=0.039).
Conclusion
Among HL patients 29-33% present with PT/INR and aPTT prolongation at diagnosis, which correlate with advanced stages, B-symptoms, and inflammation markers. This observation is of clinical importance because it prevents further unnecessary investigation. The observed negative correlation between INR and FVII, in combination with the increased levels of TFPI, suggests a possible role of TFPI in terms of excessive inhibition of TF/FVII complex. Notably, the increased levels of FII, FV, and FX correlate with inflammation markers. Taken together, the above data lead to the hypothesis that, prolonged PT/INR and aPTT are collateral findings related to disease activity and raised due to excessive activation of hemostasis in the context of thromboinflammation in HL. Similarly, the elevation of FII, FV, and FX is interpreted within thromboinflammation, which is seemingly in contrast with the prolonged PT/aPTT, suggesting an underlying compensatory mechanism.
Keyword(s): Coagulation, Hodgkin's lymphoma, Inflammation
Abstract: EP773
Type: E-Poster Presentation
Session title: Hodgkin lymphoma - Clinical
Background
Hodgkin lymphoma (HL) is characterized by an inflammatory syndrome, associated to advanced stages and B-symptoms and frequently manifested with increase in inflammation markers.
We observed in clinical practice, that HL patients frequently present at diagnosis with mild coagulation disorders, namely prolonged prothrombin time (PT) / INR and activated partial thromboplastin time (aPTT), which is not described as an established knowledge in textbooks.
Aims
We aimed to 1) analyze coagulation parameters [prothrombin time (PT), INR and activated partial thromboblastin time (aPTT)] in newly diagnosed HL patients in comparison to healthy individuals, 2) correlate them with clinical and laboratory parameters, and 3) investigate the possible underlying mechanisms.
Methods
Coagulation parameters (PT/INR, aPTT, fibrinogen, D-dimers) were determined and recorded in 80 consecutive patients with newly diagnosed HL before treatment initiation, compared to 225 healthy individuals and analyzed according to demographic data, clinical findings (histology, disease extent, IPS, B-symptoms) and laboratory parameters related to inflammation (hemoglobin, platelet and white blood cell count, ESR/CRP, albumin, α2/γ-globulins, ferritin/haptoglobin). Coagulation factors (F)II, V, VII, X and TFPI were measured in plasma and serum with ELISA, respectively, in 35/80 patients.
Results
HL patients demonstrated increased median values of all parameters compared to controls: INR 1.12 vs 0.99 (p<0.001), aPTT 37.8 vs 33.9 (p<0.001) and fibrinogen 587.5 vs 303 (p<0.001). INR was elevated (>1.2) in 28.7% of patients, aPTT (>40 sec) in 32.9%, fibrinogen (>400 mg/dL) in 83.3% and D-Dimers (>0.5 μg/ml) in 54.4%. Elevated INR/PT, aPTT, and fibrinogen were observed more frequently in patients with advanced stages (ΙΙΒ/ΙΙΙ/V) and B-symptoms. INR and aPTT correlated strongly with all inflammation markers (Spearman’s rho 0.25-0.53 and 0.26-0.38) except of leukocyte counts (and γ-globulins and ferritin for aPTT). Significantly increased levels of FII, FV and FX were observed in the majority of the patients (54.3%>88.6%), while FVII was found to be within normal limits and decreased in 1/35 patients. TFPI levels were also elevated in most cases (65.7%). A negative strong correlation between INR and FVII was noted (p<0.001). FII, FV, FX correlated with each other and with fibrinogen (p= 0.001-0.030), as well as with inflammation markers. No correlation was found between coagulation factor levels and clinical stage, B-symptoms or IPS, except the one of FX with high IPS (p=0.039).
Conclusion
Among HL patients 29-33% present with PT/INR and aPTT prolongation at diagnosis, which correlate with advanced stages, B-symptoms, and inflammation markers. This observation is of clinical importance because it prevents further unnecessary investigation. The observed negative correlation between INR and FVII, in combination with the increased levels of TFPI, suggests a possible role of TFPI in terms of excessive inhibition of TF/FVII complex. Notably, the increased levels of FII, FV, and FX correlate with inflammation markers. Taken together, the above data lead to the hypothesis that, prolonged PT/INR and aPTT are collateral findings related to disease activity and raised due to excessive activation of hemostasis in the context of thromboinflammation in HL. Similarly, the elevation of FII, FV, and FX is interpreted within thromboinflammation, which is seemingly in contrast with the prolonged PT/aPTT, suggesting an underlying compensatory mechanism.
Keyword(s): Coagulation, Hodgkin's lymphoma, Inflammation