David Green
Chicago, Illinois, United States

The year was 1967. My father had just had his prostate removed and was having considerable post-surgical pain. On the fifth post-operative day, he collapsed suddenly and could not be resuscitated. The post-mortem examination showed multiple fresh blood clots in his lungs. I was devastated but should not have been surprised. More than one hundred years earlier, the famous German pathologist Rudolph Virchow had demonstrated that clots form in the veins of the legs or pelvis of people immobilized by surgery, injuries, or illness.¹ Some or most of these clots detach from the vein and flow into the lungs where they lodge and block the circulation to the heart, often with a fatal outcome. This terrible outcome bedeviled surgery until Jacob Sharnoff, a New York State pathologist, conducted clinical trials, published papers, and wrote scores of letters to medical journals proposing changes to medical practice that have since saved countless lives.

Sharnoff (1904–1996) was born in New York but received his medical education in Vienna. He returned to New York, where he rose to the rank of clinical professor of pathology at New York Medical College and became chief of pathology at Mount Vernon Hospital. In 1956, Sharnoff observed some very large cells in the lungs of a patient dying from widespread blood clotting.² He recognized these cells as megakaryocytes, cells that are usually present in the bone marrow. Megakaryocytes produce platelets, and platelets are key participants in blood clot formation. He subsequently reported that large numbers of megakaryocytes, 10–12 per high power microscopic field, were present in the lungs of patients dying of blood clots after major operations.³

His studies of blood coagulation in such patients revealed that many had an increase in platelet counts and a shortening of the blood clotting time.⁴ Sharnoff speculated that during the stress of surgical operations, megakaryocytes were trapped in the lung and shed their platelets, enhancing blood coagulation and contributing to the formation of clots. Although this idea is logical, it is not supported by current research, which finds that only a minority of lung megakaryocytes (15%–40%) are located within blood vessels and contribute to the platelet pool.⁵ Most megakaryocytes in the lung are extravascular and appear to support inflammatory and immune responses rather than coagulation. Irrespective of the source of the hypercoagulability, Sharnoff reasoned that preventing excessive coagulation would decrease the formation of fatal clots and improve surgical outcomes.

To determine an individual’s susceptibility to excessive blood clotting, he tested each patient’s blood before surgery with a modification of the capillary clotting time.⁶ This test was performed by drawing a drop of fingertip blood into a capillary tube, incubating the tube at 37 ^°C after sealing the ends, and then snapping off a section of the tube at fifteen-second intervals until a clot was observed. The time required for the formation of the clot was recorded. Patients whose clotting times were shorter than normal were given injections of small amounts of the anticoagulant heparin. Monitoring was conducted preoperatively, immediately after operation, and daily; the heparin dose was adjusted according to the results of the testing.⁷ He reported only one death from lung clots and just two instances of excessive bleeding in 750 operations. By 1973, Sharnoff had observed only two failures (lung clots detected at autopsy) in more than 1,450 heparinizations.¹ He subsequently reported outcomes in 147 patients with hip fractures who were given subcutaneous doses of heparin on admission, preoperatively, and postoperatively until full mobilization occurred.⁸ No fatal lung clots were noted in this group, although in the years before heparin prophylaxis, the incidence of fatal clots in 403 hip fracture patients had been 3.5%.

Sharnoff established that giving heparin preoperatively saved lives by preventing accelerated clotting during surgery. His work was published in medical journals and influenced clinicians to adopt anticoagulants or mechanical methods to prevent clots in surgical and other immobilized patients. Additional scientific support has come from randomized, controlled clinical trials that abundantly confirmed the lifesaving value of prophylactic antithrombotic therapy in patients undergoing major surgery. The data from these trials are incorporated in the current American Society of Hematology guidelines on the selection of anticoagulants and mechanical methods of prophylaxis for a large variety of surgical procedures.⁹ Although the implementation of Professor Sharnoff’s methods came too late to save my father’s life, his vision and achievements have saved the lives of countless others.

References

1. Leicester J. Rudolf Virchow and the discovery of cerebral embolism. Stroke 2021; 52: e266-8.
2. Sharnoff JG. Prevention of thromboembolism. Bull NY Acad Med 1973; 49:655-60.
3. Sharnoff JG. Increased pulmonary megakaryocytes-probable role in postoperative thromboembolism. JAMA 1959; 169:688-91.
4. Sharnoff JG, Bagg JF, Breen SR, Rogiliano AG, Walsh AR, Scardino V. The possible indication of postoperative thromboembolism by platelet counts and blood coagulation studies in the patient undergoing extensive surgery. Surg Gynec Obstet 1960;111:469.
5. Puhm F, Laroche A, Bollard E. Diversity of megakaryocytes. Arterioscler Thromb Vasc Biol 2023;43:2088-98.
6. Dale HH, Laidlaw PP. A simple coagulometer. J Path Bact 1912;16:351-62.
7. Sharnoff JG, DeBlasio G. Prevention of fatal postoperative thromboembolism by heparin prophylaxis. Lancet 1970; 2:1906-07.
8. Sharnoff JG, Rosen RL, Sadler AH, Ibarra-Isunza GC. Prevention of fatal pulmonary thromboembolism by heparin prophylaxis after surgery for hip fractures. J Bone Joint Surg Am 1976;58:913-18.
9. Anderson DR, Morgano GP, Bennett C, Dentali F, Francis CW, Garcia DA, Kahn SR, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Advances 2019; 3:3898-900.