Further Studies on the “Dynia” Clotting Abnormality

Summary

1. One patient with multiple bleeding episodes and 4 asymptomatic relatives in 3 generations reveal a coagulation abnormality that cannot be attributed to any known coagulation factor deficiency or to a circulating inhibitor. The abnormality is characterized by deficient generations of intrisic thromboplastin and intermediate product I, and can be corrected by normal plasma and serum.

2. The ability of normal blood to correct the coagulation defect in vitro is heat labile; it is not removed from plasma by adsorption with BaSO₄ or Al(OH)₃. Neonatal blood and blood taken from patients either receiving coumarin drugs or with severe liver disease sustain the ability to correct the described defect. Ox, rabbit and dog blood are also corrective.

3. The finding of normal factors XII, XI and IX activities, as well as normal serum thrombosis accelerator (STA) activity, places this abnormality beyond the stage of factor IX activation.

4. The data suggest that the familial coagulation abnormality is located in the clotting sequence either in the activation of factor VIII, or in the activation of factor X by factor VIII. Either interpretation is in agreement with the finding of abnormal intermediate product I generation, which reflects primarily the intrinsic activation of factor X.

5. The frequency of this defect is unknown. Conceivably some patients considered to have factor XI (PTA) deficiency because of a plasma and serum correctable defect in their thromboplastin generation, may actually have a coagulation defect similar to that described in the Dynia family.

6. It is suggested that the name “Dynia defect” be temporarily assigned to this clotting abnormality.

^* Present Address: Department of Pathology, University of Colorado Medical Center, Denver, Colorado.

• References

• 1 Pechet L, Goldstein G, Gochios F, Deykin D. A Previously Undescribed Hereditary Clotting Abnormality. In: Diffuse Intravascular Clotting. 269-274 F. K. Schattauer; Stuttgart: 1966
• 2 Tocantins L. M. The collection of blood for studies on coagulation. in “Blood Coagulation, Hemorrhage and Thrombosis”. 2-4. Tocantins L. M, and Kazal L. A. Editors Grune and Stratton; New York-London: 1964
• 3 Salzman E. W. Measurement of platelet adhesiveness. J. Lab. clin. Med 62: 724 1963;
• 4 Pechet L. One-stage specific determination of Factor II (Prothrombin) in “Blood Coagulation, Hemorrhage and Thrombosis”. 144-147 Tocantins L. M, and Kazal L. A. Editors Grune and Stratton; New York-London: 1964
• 5 Therriault D. G, Gray J. L, Jensen H. Influence of thrombin on rate of prothrombin conversion. Proc. Soc. exp. Biol. (N. Y.) 95: 207 1957;
• 6 Ivy A. C, Shapiro P. R, Melnick P. The bleeding tendency in jaundice. Surg. Gynec. Obstet 60: 781 1935;
• 7 Duke W. W. Relation of blood platelets to hemorrhagic diseases: Description of method for determining bleeding time and coagulation time and report of three cases of hemorrhagic disease relieved by transfusion. J. A. M. A 55: 1185 1910;
• 8 Horowitz H. I, Spaet T. H. Generation of coagulation product I and its interaction with platelets and phospholipids. J. applied Phys 16: 112 1961;
• 9 Goodwin Y. F. Estimation of plasma fibrinogen. Amer. J. clin. Path 35: 227 1961;
• 10 Owren P. A. Prothrombin and accessory factors: Clinical significance. Amer. J. Med 14: 201 1953;
• 11 Pechet L. Determination of Factor VII (Proconvertin). In: “Blood Coagulation, Hemorrhage and Thrombosis,”. 213-218 Tocantins L. M, and Kazal L. A. Editors Gruñe and Stratton; New-York-London: 1964
• 12 Bachman F, Duckert F, Koller F. Stuart-Prower factor assay and its clinical significance. Thrombos. Diathes. haemorrh. (Stuttg.) 2: 24 1958;
• 13 Hardisty R. M, MacPherson J. C. A one-stage factor VIII (AHG) assay and its use on venous and capilkuy plasma. Thrombos. Diathes. haemorrh. (Stuttg.) 7: 215 1962;
• 14 Strauss L. H, Bloom G. E. Von Willebrand’s Disease: Use of platelet-adhesiveness test in diagnosis and family investigation. New Engl. J. Med 273: 111 1965;
• 15 Pool J. G, Robinson J. Assay of plasma antihemophiliac globulin (AHG). Brit. J. Haemat 5: 11 1959;
• 16 Deykin D, Wessler S. Activation product, factor IX, serum thrombotic accelerator activity, and serum-induced thrombosis. J. clin. Invest 43: 1960 1964;
• 17 Horowitz H. I, Wilcox W. P, Fujimoto M. M. Assay of plasma thromboplastin antecedent (PTA) with artificially depleted normal plasma. Blood 22: 35 1963;
• 18 Duckert F, Jung E, Schmerling D. H. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thrombos. Diathes. haemorrh. (Stuttg.) 5: 179 1960;
• 19 Colman R, Alexander B. The effect of Lanthanides and Actinides on blood coagulation. II. Assay of a new serum thromboplastin factor vulnerable to these elements and its variations in health and disease. J. clin. Invest 43: 720 1964;
• 20 Biggs R, Douglas A. S. The thromboplastin generation test. J. clin. Path 6: 23 1953;
• 21 Gaston L. W, Evanger A. E. Requirement for calcium in the thromboplastin generation test. J. Lab. clin. Med 64: 501 1964;
• 22 Goldstein G, Pechet L, Alexander B. Three-Hour Prothrombin consumption test in siliconized glass. Amer. J. clin. Path 46: 48 1966;
• 23 Rodman A. F, Barrow E. M, Graham J. B. Diagnosis and control of the hemophiloid states with the partial thromboplastin time (PTT) test. Amer. J. clin. Path 29: 525 1958;
• 24 Pascuzzi C. A, Spittel J. A, Thompson J. H, Otven C. A. Thromboplastin generation accelerator : A newly recognized component of the blood coagulation mechanism present in acute arterial occlusion complicating arteriosclerosis obliterans. J. clin. Invest 40: 1006 1961;
• 25 Rapaport S. T, Hjort P. F, Patch M. J. Further evidence that thrombin-activation of factor VIII is an essential step in intrinsic clotting. Scand. J. clin. Lab 17 (Suppl. 84) 88 1965;
• 26 Conley G. L, Ratnoff O. D, Ellicott G. E, Hartman R. G. Studies on the initiation of blood coagulation. II. An anticoagulant inhibiting the activation of plasma thromboplastic factor. J. clin. Invest 29: 1182 1950;
• 27 Kroll A, Alexander B, Cochios F, Pechet L. Hereditary deficiencies of clotting factors VII and X, associated with carotid body tumors. New Engl. J. Med 270: 6 1964;
• 28 Barrow E. M, Graham J. B. Von Willebrand’s Disease. Progress in Hematology, vol. IV 207 Moore C. V, and Brown E. B. Editors. Grune and Stratton, Publishers; New York and London: 1964
• 29 Duckert F. The prephase accelerator. Present status. Thrombos. Diathes. haemorrh. (Stuttg.) 0: 254 1961;
• 30 Butler R, Röhrig S, Siegenthaler P, Ivloeschlin S. A special haemophilic syndrome. Acta haemat. (Basel) 22: 292 1959;
• 31 Yoshida K. Haemorrhagic diathesis due to deficiency of an AHG-like factor (Nishimine Factor) associated with a qualitative platelet dysfunction. Tr. 6th Congr. Europ. Soc. Haemat. (Copenhagen 1957) 588-593 S. Karger, Publisher;
• 32 Yoshida K. The role of Tatsumi factor in an intrinsic thromboplastin formation. Proc. Xth Congr. Int’l Soc. Haemat. (Stockholm 1964). Abstract G : 62.
• 33 Connor W. E, Warner E. D, Carter J. R. A labile serum factor clotting defect: Its demonstration by thromboplastin generation test and its clinical significance. J. clin. Invest 13: 40 1961;
• 34 Hathaway W. E, Belhasen L. P, Hathaway H. S. Evidence for a new plasma thromboplastin factor. I. Case report, coagulation studies and physicochemical properties. Blood 26: 521 1965;