The aetiology of clubbing and hypertrophic osteoarthropathy.
The evidence is reviewed for the hypothesis that clubbing and hypertrophic osteoarthropathy are due to the peripheral impaction of megakaryocytes and platelet clumps in the fingers and toes, to which this particulate matter has passed in an axial stream. The normal pulmonary vascular bed retains these large particles, which fragment before entering the systemic circulation. A right-to-left shunt allows them to bypass the pulmonary vascular bed. A preliminary histological report of platelet clumps seen at necropsy in nail bed capillaries of clubbed fingers supports the hypothesis. Platelets contain and release platelet-derived growth factor, whose known effects could explain all the pathological changes in clubbing. In addition to explaining why clubbing should occur in cyanotic congenital heart disease, clubbing in sub-acute bacterial endocarditis and distal to infected arterial grafts and aneurysms can be understood in terms of platelet clumps breaking off valves or arterial walls, and passing distally. Clubbing in liver disease is associated with multiple small pulmonary arteriovenous anastomoses which allow large particles through. Hypertrophic osteoarthropathy probably shares the same mechanism, and is mainly attributable to PDGF release; but there may also be altered platelet function and an additional growth factor derived from the lungs.
Dickinson
C J
CJ
Wolfson Institute of Preventive Medicine, St. Bartholomew's Hospital Medical College, London, UK.
D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D002648:Child; D006331:Heart Diseases / Q000097:blood / Q000150:complications; D006801:Humans; D007231:Infant, Newborn; D008107:Liver Diseases / Q000097:blood / Q000150:complications; D008171:Lung Diseases / Q000097:blood / Q000150:complications; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D010005:Osteoarthropathy, Secondary Hypertrophic / Q000097:blood / Q000209:etiology* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor