Tag Archives: medicine

Bone Marrow Involvement by Cancer

16 Jun Figure 2. A breast cancer cell with two neutrophils

A 48 year old women presented with backache. The MRI suggested the presence of a metastatic involvement of multiple vertebrae. The biopsy from D11 showed it to involved by an estrogen and progesterone positive breast cancer. The X ray showed pulmonary metastasis. Treatment was initiated with combination of epirubicin, cyclophsophamide and fluorouracil with zolandronate. After the fourth cycle her haemogram showed a haemoglobin of 9.2g/dL, leucocyte count of 11.7 X 10,9/L and a platelet count of 80X109/L. and thrombocytopenia. The peripheral smear showed a differential leucocyte count was 65% polymorphonuclear neutrophils, 21% lymphocytes, 3% eosinophils, 3% monocyte, 2% myelocytes, 1% metamyelocytes and 5% band forms. Nucleated red cells were seen. A bone marrow aspiration and trephine biopsy was performed from the right iliac crest.

The aspirate was scanty and has paucity of particles. The microscopic examination showed infiltration by carcinoma. This was confirmed on the trephine biopsy. The cells were found to be expressing estrogen and progesterone receptors. The images of the bone marrow aspirate are shown below.

Figure 1. A breast carcinoma cell in the bone marrow

Figure 2. A breast carcinoma cell with two neutrophils

Figure 3. Breast carcinoma cells with an orthochromatophilic normoblast

Bone marrow involvement by cancers is common. Common cancers involving the bone marrow in adults include cancers of the breast, prostate and lung. Neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma, primitive neuroectodermal tumors and retinoblastomas are the common childhood tumors involving the bone marrow.

Bone marrow infiltration manifests with hematological anomalies. Leucoerythroblastic anaemia when present is most suggestive of bone marrow involvement. It is neither sensitive nor specific and is absent in about half the patients. About 70% of the patients have concomitant bone involvement and symptoms of metastatic bone disease – bone pain, fractures and hypercalcaemia may be present.

The diagnosis is made by a bone marrow aspiration and biopsy. Sensitivity of bone marrow aspiration for diagnosing bone marrow involvement be cancer is  28% and that of trephine biopsy is 35-45%. The diagnostic yields are better  increased by examining more films examinations of clotted areas, taking multiple biopsies or one large biopsy; 75% of the trephine biopsies show aspirate positive; she patients show normal trephine and abnormal cells on the smear; both should be performed

Bone marrow involvement has been shown to be an adverse prognostic marker for breast cancer. The impact of bone marrow involvement in other cancers in not known. Bone marrow cells can survive chemotherapy and remain dormant for long periods (Int J Cancer 2008 Nov 1;123(9):1991-2006). The role of bone marrow metastasis in other cancers is not clear though there are suggestions that they may affect prognosis of prostate cancer (Adv Urol. 2012; 2012: 135281) colorectal cancer (Br J Cancer  2011 Apr 26;104(9):1434-9)

Manifestations:

Circulating tumor cells were first reposted by ash worth in 1869.

Immunomagnetic capture using antibodies against epithelial cell surface molecule EpCam

SWOG conducting a study to determine the utility of changing therepay of breast cancer depending on the response of CTC to one cycle of chemotherapy

Bleeding Time

1 Jun

Figure 1. Components of the homeostatic system Haemeostasis involves an interaction between the coagulation system, platelets and the vessel wall. Coagulation defects are screened by the prothrombin time, activated partial thromboplastin time and thrombin time. If activation of coagulation is prevented (by blotting blood with a filter paper) and vessels are not allowed to contract by occluding venous flow hemostasis will depend on vessel wall and platelet function. The bleeding time  that is based on this principle was proposed as a screening test for defects in homeostatic functions of the vessel wall and platelets.

Though bleeding time was described by Milan in 1901, Duke, who described the earlobe test in 1910,  demonstrated that the bleeding time was prolonged by thrombocytopenia and corrected by transfusion of whole blood that increased platelet count. Ivy, a surgeon observed that bleeding time by the Duke’s method was normal in many patients with jaundice. He attributed this to variability in the “tone” of capillaries. He modified the bleeding time by applying a standard pressure with a sphygmomanometer cuff proximal to the test wound to counter the interpatinet variability in capillary “tone”. Ivy’s method eventually became the standard method. The bleeding time appeared to be a clinically useful test. One of the greatest concerns of a surgeon is peri-operative bleeding. The purpose of bleeding time was to asses the platelet and vessel wall function and provide the surgeon with safety net. It was shown that the bleeding time correlated with platelet count. The incidence of bleeding in patient with idiopathic thrombocytopaenic purpura is less for the platelet count and patients with uraemia may bleed even with normal counts. Bleeding time was shown to be shorter than expected form platelet count in idiopathic thrombocytopaenic purpura and longer than expected form platelet counts in patients with uremia suggesting that it could mirror in vivo platelet function. The simplicity and the apparent usefulness of bleeding time made it a popular test for screening and diagnosis of bleeding disorders.

Bleeding time was never systemically evaluated. Studies evaluating bleeding time began to appear 1984. The characteristics of a test include sensitivity, specificity, positive predictive value and negative predictive value. These have never been determined for bleeding time. Bleeding time failed to predict bleeding leading to discontinuation of the practice of performance of pre-opertive bleeding time. In more damming evidence the discontinuation of bleeding time has not been found to increase the incidence of post-operative bleeding. An important assumption of bleeding time is  that skin bleeding time co-relates with tissue bleeding time. No relation has however been  found between skin and brain bleeding time in rats.

How is Bleeding Time Performed?
Bleeding time is performed by the Ivy’s method. The sphygmomanometer cuff is inflated to a presure of 40mm of Hg and maintined at that throughout the test. Using a standardized divice a cut is made on the dorsal aspect of the forarm avoiding scars and veins. The blood is blotted every 30 seconds using a filter paper avioding touching the wound with the filter paper. Bleeding time is the time taken for the bleeding to stop. If bleeding does not stop by 20 minutes the cuff is deflated and haemostasis is achieved by applying pressure. The bleeding time leaves a scar on the forearm and this is an issue in patients with a tendency to form keloids. The bleeding time is often performed by measuring the time taken for bleeding to stop following puncture of fingertip by a hypodermic needle. This not standardized and is inappropriate.

Limitations of the Bleeding Time
Bleeding time has not been found to be useful for screening for bleeding or for the diagnosis of bleeding disorders. Bleeding time is of limited value in von Willebrand’s disease, a common bleeding disorder. Half the patinets with von Willebrand’s disease have a normal bleeding time.  Even when prolonged, the bleeding time shows a day to day variability in the same patient. The coefficient of variation of the test is 15%. Given the numerous interactions between platelet, vessel wall and the coagulation system, the seperation between the components of haemostasis is artificial. Patients with hemophilia, a coagulation disease, have a prolonged bleeding time and heparin may increase bleeding time.

Place of Bleeding Time in Clinical Practice
Bleeding time should not be performed to asses haemostasis. The starting point to investigate a bleeding patient is a combination of prothrombin time, activated partial thromboplastin time, thrombin time and platelet count. Platelet count, morphology and function tests should be used to asses platelet function. The concept behind bleeding time is appealing better methods are needed to test the concept.

 

 

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