- Atherosclerosis (HP:0002621): A condition characterized by patchy atheromas or atherosclerotic plaques which develop in the walls of medium-sized and large arteries and can lead to arterial stenosis with reduced or blocked blood flow. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Hypoplasia of the nasal bone (HP:0004646): Underdevelopment of the nasal bone. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Joint hemorrhage (HP:0005261): Hemorrhage occurring within a joint. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Shortening of all distal phalanges of the fingers (HP:0006118): Hypoplasia of all of the distal phalanx of finger. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Epiphyseal stippling (HP:0010655): The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Prolonged bleeding following procedure (HP:0011890): Prolonged or protracted bleeding following an invasive procedure or intervention. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Post-partum hemorrhage (HP:0011891): Significant maternal hemorrhage/blood loss following deilvery of a child. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Cephalohematoma (HP:0012541): Hemorrhage between the skull and periosteum of a newborn resulting from rupture of blood vessels that cross the periosteum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Prolonged bleeding following circumcision (HP:0030137): Bleeding that persists for a longer than usual time following circumcision. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Ecchymosis (HP:0031364): A purpuric lesion that is larger than 1 cm in diameter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98434)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98434)
- Gastrointestinal hemorrhage (HP:0002239): Hemorrhage affecting the gastrointestinal tract. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98434)
- Pulmonary artery stenosis (HP:0004415): An abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98434)
- Abnormal umbilical stump bleeding (HP:0011884): Abnormal bleeding of the umbilical stump following separation of the cord at approximately 7-10 days after birth. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:98434)
- Bruising susceptibility (HP:0000978): An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Abnormal bleeding (HP:0001892): An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Prolonged partial thromboplastin time (HP:0003645): Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Reduced protein S activity (HP:0004855): An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein S. Protein S is a cofactor of protein C. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Reduced protein C activity (HP:0005543): An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein C. Protein C is activated to protein Ca by thrombin bound to thrombomodulin. Activated protein C degrades factors VIIIa and Va. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Prolonged prothrombin time (HP:0008151): Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Reduced factor VII activity (HP:0008169): Reduced activity of coagulation factor VII. Factor VII is part of the extrinsic coagulation pathway, which is initiated at the site of injury in response to the release of tissue factor (fIII). Tissue factor and activated factor VII catalyze the activation of factor X. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Reduced factor X activity (HP:0008321): Reduced activity of coagulation factor X. The extrinsic and intrinsic pathways converge at factor X (fX). The extrinsic pathway activates fX by means of d factor VII with its cofactor, tissue factor. The intrinsic pathway activates fX by means of the tenase complex (Ca2+ and factors VIIIa, IXa and X) on the surface of activated platelets. Factor Xa in turn activates prothrombin (factor II) to thrombin (factor IIa). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Reduced factor IX activity (HP:0011858): Decreased activity of coagulation factor IX. Factor IX, which itself is activated by factor Xa or factor VIIa to form factor IXa, activates factor X into factor Xa. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Decreased level of heparin co-factor II (HP:0040226): An abnormality of coagulation related to a decreased concentration of heparin co-factor II. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:98434)
- Menorrhagia (HP:0000132): Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Epistaxis (HP:0000421): Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Cutis laxa (HP:0000973): Wrinkled, redundant, inelastic and sagging skin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Angioid streaks (HP:0001102): Irregular lines in the outer retina and Bruch membrane that are typically configured in a radiating fashion and emanate from the optic disc. Angioid streaks are crack-like dehiscences in abnormally thickened and calcified Bruch membrane, resulting in atrophy of the overlying retinal pigment epithelium. They may be associated with a number of endocrine, metabolic, and connective tissue abnormalities but can be idiopathic. They can be associated with neovascular complexes (choroid). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
- Intracranial hemorrhage (HP:0002170): Hemorrhage occurring within the skull. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:98434)
These phenotypes are associated with the disease Hereditary combined deficiency of vitamin K-dependent clotting factors (ORPHA:98434).