Abstract

The blood supply of the bone and bone marrow are interconnected through a network of vessels. Arteries penetrating the bone flow into the marrow cavity while blood from marrow sinuses and veins leave the tissue via the bone. The current study was designed to search for thrombosis in the small blood vessels of bone and bone marrow. Bone biopsies of 40 patients were studied using specific staining to fibrin with martin scarlet blue (MSB) and by immune-staining to tissue factor (TF), TF pathway inhibitor and heparanase that is a pro-angiogenic and pro-coagulant protein. Biopsies included: ten cases of bone metastasis from carcinoma origin, ten cases of avascular necrosis (AVN) of femur head and ten cases of osteoarthrosis of femur head. Ten cases with diffuse large cell lymphoma without bone or bone marrow involvement were the control group. Vessels density was higher in the bone and bone marrow of metastasis, AVN and osteoarthrosis biopsies compared to controls (P<0.001). Thrombi were documented in the bone and bone marrow of metastasis (5/10), AVN (6/10) and osteoarthrosis (6/10) biopsies and were absent in the controls. Staining of TF, TFPI and heparanase were more prominent, mainly in the blood vessels, in the biopsies of metastasis, AVN and osteoarthrosis compared to controls. The present study demonstrates for the first time thrombosis in the microcirculation of bone and bone marrow that can potentially contribute to patients bone pain. Increased level of TF and heparanase may contribute to the procoagulant and pro-angiogenic state. Intervention with anticoagulant drugs to prevent bone pain should be further evaluated.

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